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Devendra T. Mourya - One of the best experts on this subject based on the ideXlab platform.
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highly infectious tick borne viral diseases kyasanur forest disease and crimean congo haemorrhagic fever in india
2014Co-Authors: Devendra T. Mourya, Pragya D. Yadav, Deepak Y. PatilAbstract:Ticks are distributed worldwide and can harbour and transmit a range of pathogenic microorganisms that affect livestock and humans. Most Tick-Borne diseases are caused by Tick-Borne Viruses. Two major Tick-Borne Virus zoonotic diseases, Kyasanur forest disease (KFD) and Crimean–Congo haemorrhagic fever (CCHF), are notifiable in India and are associated with high mortality rates. KFD Virus was first identified in 1957 in Karnataka state; the tick Haemaphysalis spinigera is the main vector. During 2012–2013, cases were reported from previously unaffected areas in Karnataka, and newer areas of Kerala and Tamil Nadu states. These reports may be the result of improved active surveillance or may reflect altered Virus transmission because of environmental change. CCHF is distributed in Asia, Africa and some part of Europe; Hyalomma spp. ticks are the main vectors. The existence of CCHF in India was first confirmed in 2011 in Gujarat state. In 2013, a non-nosocomial CCHF outbreak in Amreli district, as well as positive tick, animal and human samples in various areas of Gujarat state, suggested that the Virus is widespread in Gujarat state, India. The emergence of KFD and CCHF in various Indian states emphasizes the need for nationwide surveillance among animals and humans. There is a need for improved diagnostic facilities, more containment laboratories, better public awareness, and implementation of thorough tick control in affected areas during epidemics.
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Expediency of dengue illness classification: the Sri Lankan perspective Highly infectious Tick-Borne viral diseases: Kyasanur forest disease and Crimean-Congo haemorrhagic fever in India.
WHO South-East Asia journal of public health, 2014Co-Authors: Devendra T. Mourya, Pragya D. Yadav, Deepak Y. PatilAbstract:Ticks are distributed worldwide and can harbourand transmit a range of pathogenic microorganisms that affect livestock and humans. Most Tick-Borne diseases are caused by Tick-Borne Viruses. Two major Tick-Borne Virus zoonotic diseases, Kyasanur forest disease (KFD) and Crimean-Congo haemorrhagic fever (CCHF), are notifiable in India and are associated with highmortality rates. KFD Virus was first identified in 1957 in Karnataka state; the tick Haemaphysalis spinigera is the main vector. During 2012-2013, cases were reported from previouslyunaffected areas in Karnataka, and newer areas of Kerala and Tamil Nadu states. These reports may be the result of improved active surveillance or may reflect altered Virus transmission because of environmental change. CCHF is distributed in Asia, Africa and some part of Europe; Hyalomma spp. ticks are the main vectors. The existence of CCHF in India was first confirmed in 2011 in Gujaratstate. In 2013, a non-nosocomial CCHF outbreak in Amreli district, as well as positive tick, animal and human samples in various areas of Gujarat state, suggested that the Virus is widespread in Gujarat state, India. The emergence of KFDand CCHF in various Indian states emphasizes the need for nationwide surveillance among animals and humans. There is a need for improved diagnostic facilities, more containment laboratories, better public awareness, and implementation ofthorough tick control in affected areas during epidemics.
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genomic analysis reveals nairobi sheep disease Virus to be highly diverse and present in both africa and in india in the form of the ganjam Virus variant
Infection Genetics and Evolution, 2011Co-Authors: Charuta Kale, Martin J. Vincent, Marina L. Khristova, Pragya D. Yadav, Akhilesh C. Mishra, Stuart T. Nichol, Devendra T. MouryaAbstract:Abstract Nairobi sheep disease (NSD) Virus, the prototype Tick-Borne Virus of the genus NairoVirus, family Bunyaviridae is associated with acute hemorrhagic gastroenteritis in sheep and goats in East and Central Africa. The closely related Ganjam Virus found in India is associated with febrile illness in humans and disease in livestock. The complete S, M and L segment sequences of Ganjam and NSD Virus and partial sequence analysis of Ganjam viral RNA genome S, M and L segments encoding regions (396 bp, 701 bp and 425 bp) of the viral nucleocapsid (N), glycoprotein precursor (GPC) and L polymerase (L) proteins, respectively, was carried out for multiple Ganjam Virus isolates obtained from 1954 to 2002 and from various regions of India. M segments of NSD and Ganjam Virus encode a large ORF for the glycoprotein precursor (GPC), (1627 and 1624 amino acids in length, respectively) and their L segments encode a very large L polymerase (3991 amino acids). The complete S, M and L segments of NSD and Ganjam Viruses were more closely related to one another than to other characterized nairoViruses, and no evidence of reassortment was found. However, the NSD and Ganjam Virus complete M segment differed by 22.90% and 14.70%, for nucleotide and amino acid respectively, and the complete L segment nucleotide and protein differing by 9.90% and 2.70%, respectively among themselves. Ganjam and NSD Virus, complete S segment differed by 9.40–10.40% and 3.2–4.10 for nucleotide and proteins while among Ganjam Viruses 0.0–6.20% and 0.0–1.4%, variation was found for nucleotide and amino acids. Ganjam Virus isolates differed by up to 17% and 11% at the nucleotide level for the partial S and L gene fragments, respectively, with less variation observed at the deduced amino acid level (10.5 and 2%, S and L, respectively). However, the Virus partial M gene fragment (which encodes the hypervariable mucin-like domain) of these Viruses differed by as much as 56% at the nucleotide level. Phylogenetic analysis of partial sequence differences suggests considerable mixing and movement of Ganjam Virus strains within India, with no clear relationship between genetic lineages and Virus geographic origin or year of isolation. Surprisingly, NSD Virus does not represent a distinct lineage, but appears as a variant with other Ganjam Virus among NSD Virus group.
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recent ancestry of kyasanur forest disease Virus
Emerging Infectious Diseases, 2009Co-Authors: Rajeev Mehla, Serena A Carroll, Prasanna N. Yergolkar, Pragya D. Yadav, Akhilesh C. Mishra, Bobbie R. Erickson, Stuart T. Nichol, Pradip V. Barde, Sandeep Kumar, Devendra T. MouryaAbstract:Kyasanur Forest disease Virus (KFDV) is a member of the mammalian Tick-Borne Virus group (previously referred to as the Tick-Borne encephalitis serogroup) of the family Flaviviridae and genus FlaviVirus (1). In addition to KFDV, this group contains Louping ill, Tick-Borne encephalitis, Omsk hemorrhagic fever, Langat, Powassan, Royal Farm, and Gadgets Gully Viruses. KFD was first recognized in 1957 in the Kyasanur Forest of Shimoga District, Karnataka State, India, when a disease causing a high number of deaths was observed in 2 species of monkeys: the black-faced langur (Semnopithecus entellus, earlier known as Presbytis entellus) and the red-faced bonnet monkey (Macaca radiata). Human cases were also found among persons who visited forests to collect firewood, grass, and other forest products. Human disease is characterized by an incubation period of ≈3–8 days, followed by chills, frontal headache, body ache, and high fever for 5–12 days, and a case-fatality rate >30% (2). During infection by KFDV, Virus titer remains high <10 days after onset of symptoms, as reported by Bhat et al. (3). However, Upadhyaya et al. (4) found that viremia in patients lasted for 12–13 days of illness and unlike most other flaviViruses, remains high during the first 3–6 days with titers as high as 3.1 × 106 PFU/mL. Continuing deaths in monkeys and an average of 400–500 human cases have been seen annually over the past 5 decades, commonly occurring in evergreen, semi-evergreen, and neighboring, moist, deciduous forest areas. An array of tick species, mainly Haemaphysalis spinigera, act as vectors for KFDV (5). This species of tick is widely distributed in tropical evergreen and deciduous forests of southern and central India and Sri Lanka. KFDV has also been isolated from 7 other species of this genus and from Dermacentor and Ixodes ticks. This disease is transmitted by ticks among ground birds and small mammals such as the white-tailed rat, white-bellied rat, shrew, and bat. High titers of Virus can be obtained after experimental infection of black-napped hares, porcupines, flying squirrels, Malabar giant squirrels, three-striped squirrels, gerbils, mice, long-tailed tree mice, and shrews (2–9). Until 1971, KFDV was endemic to the Sagar, Sorab, and Shikaripur taluks (counties) of Shimoga District (Figure 1). By 1972, a new focus of Virus activity appeared in Sirsi Taluk, Uttara Kannada District. Many KFDV isolates were obtained from Karnataka during 1957–1972 and maintained in a repository at the National Institute of Virology (NIV) in Pune, India. However, the Virus was found to be highly infectious, as shown by numerous infections in field and laboratory personnel (2,10), which resulted in suspension of work with this Virus until an appropriate BioSafety Level-3 laboratory was built at NIV in 2004. In 2006, this laboratory isolated a Virus from a serum sample of a patient suspected of having KFD that was obtained from the Virus Diagnostic Laboratory in Shimoga. Figure 1 Areas of Karnataka State, India, known to be affected by Kyasanur Forest disease (dark gray shading). More recent studies have identified KFDV in Saudi Arabia and the People’s Republic of China (11,12). During 1994–1995, a Virus was isolated from hemorrhagic fever patients in the Makkah region of Saudi Arabia and identified as a KFDV variant, referred to as the Alkhurma variant or subgroup (11,13,14). The prototype strain of KFDV from Saudi Arabia (strain 1176, isolated in 1995) and the KFDV reference strain from India (P-9605, isolated in 1957) differ from each another by only 8% at the genome nucleotide level, despite their temporal (38 years) and geographic (≈4,000 km) separation. A Virus initially referred to as Nanjianyin Virus, isolated in 1989 from a febrile patient in Nanjian County in the Hengduan Mountain region of Yunnan Province in southwestern China, was recently identified as a strain of KFDV (12). However, it is unclear whether this KFDV 1989 isolate from China is an authentic Virus isolate because it is virtually identical at the nucleotide level with the 1957 reference strain from India (P-9605), despite their being isolated 32 years and almost 3,000 km apart. The P-9605 strain was distributed widely to arboVirus reference laboratories. Reference KFDV Virus was used as part of the analysis of serum samples from Yunnan Province (15,16). Results of molecular epidemiologic studies have suggested that Tick-Borne flaviViruses have evolved slowly while dispersing north and west across Asian and European forests during the past few millennia (17–19). This pattern is different from that of rapidly evolving mosquito-borne flaviViruses, many of which can be transported long distances by migratory birds, persons, animals, or mosquito eggs (19,20). We examined the diversity and evolution of KFDV and present data that indicated that KFDV isolates from India, Saudi Arabia, and China share a recent common ancestor, indicating long-range movement of this Tick-Borne flaviVirus. In addition, we also estimated the evolution rate of KFDV and compared it with that of mosquito-borne flaviViruses.
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Recent ancestry of Kyasanur forest disease Virus. Emerg Infect Dis 15
2009Co-Authors: Rajeev Mehla, Serena A Carroll, Prasanna N. Yergolkar, Akhilesh C. Mishra, Bobbie R. Erickson, Stuart T. Nichol, Eep R. P. Kumar, Pragya Yadav, Pradip V. Barde, Devendra T. MouryaAbstract:Kyasanur Forest disease Virus (KFDV) is enzootic to India and maintained in ticks, mammals, and birds. It causes severe febrile illness in humans and was first recognized in 1957 associated with a high number of deaths among monkeys in Kyasanur Forest. Genetic analysis of 48 Viruses isolated in India during 1957–2006 showed low diversity (1.2%). Bayesian coalescence analysis of these sequences and those of KFDVs from Saudi Arabia and the People’s Republic of China estimated that KFDVs have evolved at a mean rate of ≈6.4 × 10 –4 substitutions/site/year, which is similar to rates estimated for mosquito-borne flaviViruses. KFDVs were estimated to have shared a common ancestor in ≈1942, fifteen years before identification of the disease in India. These data are consistent with the view that KFD represented a newly emerged disease when first recognized. Recent common ancestry of KFDVs from India and Saudi Arabia, despite their large geographic separation, indicates long-range movement of Virus, possibly by birds. Kyasanur Forest disease Virus (KFDV) is a member of the mammalian Tick-Borne Virus group (previously referred to as the Tick-Borne encephalitis serogroup) of the family Flaviviridae and genus FlaviVirus (1). In addition to KFDV, this group contains Louping ill, Tick-Borne encephalitis, Omsk hemorrhagic fever, Langat, Powassan, Royal Farm, and Gadgets Gully Viruses. KFD was first recognized in 1957 in the Kyasanur Forest of Shimoga District, Karnataka State, India, when a disease causing a high number of deaths was observed in 2 species of monkeys: the black-faced langur (Semnopithecus entellus, earlier know
Pragya D. Yadav - One of the best experts on this subject based on the ideXlab platform.
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highly infectious tick borne viral diseases kyasanur forest disease and crimean congo haemorrhagic fever in india
2014Co-Authors: Devendra T. Mourya, Pragya D. Yadav, Deepak Y. PatilAbstract:Ticks are distributed worldwide and can harbour and transmit a range of pathogenic microorganisms that affect livestock and humans. Most Tick-Borne diseases are caused by Tick-Borne Viruses. Two major Tick-Borne Virus zoonotic diseases, Kyasanur forest disease (KFD) and Crimean–Congo haemorrhagic fever (CCHF), are notifiable in India and are associated with high mortality rates. KFD Virus was first identified in 1957 in Karnataka state; the tick Haemaphysalis spinigera is the main vector. During 2012–2013, cases were reported from previously unaffected areas in Karnataka, and newer areas of Kerala and Tamil Nadu states. These reports may be the result of improved active surveillance or may reflect altered Virus transmission because of environmental change. CCHF is distributed in Asia, Africa and some part of Europe; Hyalomma spp. ticks are the main vectors. The existence of CCHF in India was first confirmed in 2011 in Gujarat state. In 2013, a non-nosocomial CCHF outbreak in Amreli district, as well as positive tick, animal and human samples in various areas of Gujarat state, suggested that the Virus is widespread in Gujarat state, India. The emergence of KFD and CCHF in various Indian states emphasizes the need for nationwide surveillance among animals and humans. There is a need for improved diagnostic facilities, more containment laboratories, better public awareness, and implementation of thorough tick control in affected areas during epidemics.
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Expediency of dengue illness classification: the Sri Lankan perspective Highly infectious Tick-Borne viral diseases: Kyasanur forest disease and Crimean-Congo haemorrhagic fever in India.
WHO South-East Asia journal of public health, 2014Co-Authors: Devendra T. Mourya, Pragya D. Yadav, Deepak Y. PatilAbstract:Ticks are distributed worldwide and can harbourand transmit a range of pathogenic microorganisms that affect livestock and humans. Most Tick-Borne diseases are caused by Tick-Borne Viruses. Two major Tick-Borne Virus zoonotic diseases, Kyasanur forest disease (KFD) and Crimean-Congo haemorrhagic fever (CCHF), are notifiable in India and are associated with highmortality rates. KFD Virus was first identified in 1957 in Karnataka state; the tick Haemaphysalis spinigera is the main vector. During 2012-2013, cases were reported from previouslyunaffected areas in Karnataka, and newer areas of Kerala and Tamil Nadu states. These reports may be the result of improved active surveillance or may reflect altered Virus transmission because of environmental change. CCHF is distributed in Asia, Africa and some part of Europe; Hyalomma spp. ticks are the main vectors. The existence of CCHF in India was first confirmed in 2011 in Gujaratstate. In 2013, a non-nosocomial CCHF outbreak in Amreli district, as well as positive tick, animal and human samples in various areas of Gujarat state, suggested that the Virus is widespread in Gujarat state, India. The emergence of KFDand CCHF in various Indian states emphasizes the need for nationwide surveillance among animals and humans. There is a need for improved diagnostic facilities, more containment laboratories, better public awareness, and implementation ofthorough tick control in affected areas during epidemics.
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genomic analysis reveals nairobi sheep disease Virus to be highly diverse and present in both africa and in india in the form of the ganjam Virus variant
Infection Genetics and Evolution, 2011Co-Authors: Charuta Kale, Martin J. Vincent, Marina L. Khristova, Pragya D. Yadav, Akhilesh C. Mishra, Stuart T. Nichol, Devendra T. MouryaAbstract:Abstract Nairobi sheep disease (NSD) Virus, the prototype Tick-Borne Virus of the genus NairoVirus, family Bunyaviridae is associated with acute hemorrhagic gastroenteritis in sheep and goats in East and Central Africa. The closely related Ganjam Virus found in India is associated with febrile illness in humans and disease in livestock. The complete S, M and L segment sequences of Ganjam and NSD Virus and partial sequence analysis of Ganjam viral RNA genome S, M and L segments encoding regions (396 bp, 701 bp and 425 bp) of the viral nucleocapsid (N), glycoprotein precursor (GPC) and L polymerase (L) proteins, respectively, was carried out for multiple Ganjam Virus isolates obtained from 1954 to 2002 and from various regions of India. M segments of NSD and Ganjam Virus encode a large ORF for the glycoprotein precursor (GPC), (1627 and 1624 amino acids in length, respectively) and their L segments encode a very large L polymerase (3991 amino acids). The complete S, M and L segments of NSD and Ganjam Viruses were more closely related to one another than to other characterized nairoViruses, and no evidence of reassortment was found. However, the NSD and Ganjam Virus complete M segment differed by 22.90% and 14.70%, for nucleotide and amino acid respectively, and the complete L segment nucleotide and protein differing by 9.90% and 2.70%, respectively among themselves. Ganjam and NSD Virus, complete S segment differed by 9.40–10.40% and 3.2–4.10 for nucleotide and proteins while among Ganjam Viruses 0.0–6.20% and 0.0–1.4%, variation was found for nucleotide and amino acids. Ganjam Virus isolates differed by up to 17% and 11% at the nucleotide level for the partial S and L gene fragments, respectively, with less variation observed at the deduced amino acid level (10.5 and 2%, S and L, respectively). However, the Virus partial M gene fragment (which encodes the hypervariable mucin-like domain) of these Viruses differed by as much as 56% at the nucleotide level. Phylogenetic analysis of partial sequence differences suggests considerable mixing and movement of Ganjam Virus strains within India, with no clear relationship between genetic lineages and Virus geographic origin or year of isolation. Surprisingly, NSD Virus does not represent a distinct lineage, but appears as a variant with other Ganjam Virus among NSD Virus group.
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recent ancestry of kyasanur forest disease Virus
Emerging Infectious Diseases, 2009Co-Authors: Rajeev Mehla, Serena A Carroll, Prasanna N. Yergolkar, Pragya D. Yadav, Akhilesh C. Mishra, Bobbie R. Erickson, Stuart T. Nichol, Pradip V. Barde, Sandeep Kumar, Devendra T. MouryaAbstract:Kyasanur Forest disease Virus (KFDV) is a member of the mammalian Tick-Borne Virus group (previously referred to as the Tick-Borne encephalitis serogroup) of the family Flaviviridae and genus FlaviVirus (1). In addition to KFDV, this group contains Louping ill, Tick-Borne encephalitis, Omsk hemorrhagic fever, Langat, Powassan, Royal Farm, and Gadgets Gully Viruses. KFD was first recognized in 1957 in the Kyasanur Forest of Shimoga District, Karnataka State, India, when a disease causing a high number of deaths was observed in 2 species of monkeys: the black-faced langur (Semnopithecus entellus, earlier known as Presbytis entellus) and the red-faced bonnet monkey (Macaca radiata). Human cases were also found among persons who visited forests to collect firewood, grass, and other forest products. Human disease is characterized by an incubation period of ≈3–8 days, followed by chills, frontal headache, body ache, and high fever for 5–12 days, and a case-fatality rate >30% (2). During infection by KFDV, Virus titer remains high <10 days after onset of symptoms, as reported by Bhat et al. (3). However, Upadhyaya et al. (4) found that viremia in patients lasted for 12–13 days of illness and unlike most other flaviViruses, remains high during the first 3–6 days with titers as high as 3.1 × 106 PFU/mL. Continuing deaths in monkeys and an average of 400–500 human cases have been seen annually over the past 5 decades, commonly occurring in evergreen, semi-evergreen, and neighboring, moist, deciduous forest areas. An array of tick species, mainly Haemaphysalis spinigera, act as vectors for KFDV (5). This species of tick is widely distributed in tropical evergreen and deciduous forests of southern and central India and Sri Lanka. KFDV has also been isolated from 7 other species of this genus and from Dermacentor and Ixodes ticks. This disease is transmitted by ticks among ground birds and small mammals such as the white-tailed rat, white-bellied rat, shrew, and bat. High titers of Virus can be obtained after experimental infection of black-napped hares, porcupines, flying squirrels, Malabar giant squirrels, three-striped squirrels, gerbils, mice, long-tailed tree mice, and shrews (2–9). Until 1971, KFDV was endemic to the Sagar, Sorab, and Shikaripur taluks (counties) of Shimoga District (Figure 1). By 1972, a new focus of Virus activity appeared in Sirsi Taluk, Uttara Kannada District. Many KFDV isolates were obtained from Karnataka during 1957–1972 and maintained in a repository at the National Institute of Virology (NIV) in Pune, India. However, the Virus was found to be highly infectious, as shown by numerous infections in field and laboratory personnel (2,10), which resulted in suspension of work with this Virus until an appropriate BioSafety Level-3 laboratory was built at NIV in 2004. In 2006, this laboratory isolated a Virus from a serum sample of a patient suspected of having KFD that was obtained from the Virus Diagnostic Laboratory in Shimoga. Figure 1 Areas of Karnataka State, India, known to be affected by Kyasanur Forest disease (dark gray shading). More recent studies have identified KFDV in Saudi Arabia and the People’s Republic of China (11,12). During 1994–1995, a Virus was isolated from hemorrhagic fever patients in the Makkah region of Saudi Arabia and identified as a KFDV variant, referred to as the Alkhurma variant or subgroup (11,13,14). The prototype strain of KFDV from Saudi Arabia (strain 1176, isolated in 1995) and the KFDV reference strain from India (P-9605, isolated in 1957) differ from each another by only 8% at the genome nucleotide level, despite their temporal (38 years) and geographic (≈4,000 km) separation. A Virus initially referred to as Nanjianyin Virus, isolated in 1989 from a febrile patient in Nanjian County in the Hengduan Mountain region of Yunnan Province in southwestern China, was recently identified as a strain of KFDV (12). However, it is unclear whether this KFDV 1989 isolate from China is an authentic Virus isolate because it is virtually identical at the nucleotide level with the 1957 reference strain from India (P-9605), despite their being isolated 32 years and almost 3,000 km apart. The P-9605 strain was distributed widely to arboVirus reference laboratories. Reference KFDV Virus was used as part of the analysis of serum samples from Yunnan Province (15,16). Results of molecular epidemiologic studies have suggested that Tick-Borne flaviViruses have evolved slowly while dispersing north and west across Asian and European forests during the past few millennia (17–19). This pattern is different from that of rapidly evolving mosquito-borne flaviViruses, many of which can be transported long distances by migratory birds, persons, animals, or mosquito eggs (19,20). We examined the diversity and evolution of KFDV and present data that indicated that KFDV isolates from India, Saudi Arabia, and China share a recent common ancestor, indicating long-range movement of this Tick-Borne flaviVirus. In addition, we also estimated the evolution rate of KFDV and compared it with that of mosquito-borne flaviViruses.
Stuart T. Nichol - One of the best experts on this subject based on the ideXlab platform.
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single dose replicon particle vaccine provides complete protection against crimean congo hemorrhagic fever Virus in mice
Emerging microbes & infections, 2019Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Brendan T. Freitas, Markus H. Kainulainen, Joann D Colemanmccray, Eric BergeronAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is an emerging Tick-Borne Virus from the family Nairoviridae that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution,...
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structure function and evolution of the crimean congo hemorrhagic fever Virus nucleocapsid protein
Journal of Virology, 2012Co-Authors: Stephen D Carter, Stuart T. Nichol, Rebecca Surtees, Thomas A. Edwards, Eric Bergeron, Cheryl T Walter, Antonio Ariza, Julian A Hiscox, John N. BarrAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is an emerging Tick-Borne Virus of the Bunyaviridae family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 A. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that of the recently reported N protein from strain YL04057 shows a close correspondence of all folds but significant transposition of the arm through a rotation of 180 degrees and a translation of 40 A. These observations suggest a structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding and oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally critical residues within these domains were identified using a minigenome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif; however, the cleaved N protein remains an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyaVirus but the arenaVirus Lassa Virus instead, suggesting that current segmented negative-strand RNA Virus taxonomy may need revision.
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genomic analysis reveals nairobi sheep disease Virus to be highly diverse and present in both africa and in india in the form of the ganjam Virus variant
Infection Genetics and Evolution, 2011Co-Authors: Charuta Kale, Martin J. Vincent, Marina L. Khristova, Pragya D. Yadav, Akhilesh C. Mishra, Stuart T. Nichol, Devendra T. MouryaAbstract:Abstract Nairobi sheep disease (NSD) Virus, the prototype Tick-Borne Virus of the genus NairoVirus, family Bunyaviridae is associated with acute hemorrhagic gastroenteritis in sheep and goats in East and Central Africa. The closely related Ganjam Virus found in India is associated with febrile illness in humans and disease in livestock. The complete S, M and L segment sequences of Ganjam and NSD Virus and partial sequence analysis of Ganjam viral RNA genome S, M and L segments encoding regions (396 bp, 701 bp and 425 bp) of the viral nucleocapsid (N), glycoprotein precursor (GPC) and L polymerase (L) proteins, respectively, was carried out for multiple Ganjam Virus isolates obtained from 1954 to 2002 and from various regions of India. M segments of NSD and Ganjam Virus encode a large ORF for the glycoprotein precursor (GPC), (1627 and 1624 amino acids in length, respectively) and their L segments encode a very large L polymerase (3991 amino acids). The complete S, M and L segments of NSD and Ganjam Viruses were more closely related to one another than to other characterized nairoViruses, and no evidence of reassortment was found. However, the NSD and Ganjam Virus complete M segment differed by 22.90% and 14.70%, for nucleotide and amino acid respectively, and the complete L segment nucleotide and protein differing by 9.90% and 2.70%, respectively among themselves. Ganjam and NSD Virus, complete S segment differed by 9.40–10.40% and 3.2–4.10 for nucleotide and proteins while among Ganjam Viruses 0.0–6.20% and 0.0–1.4%, variation was found for nucleotide and amino acids. Ganjam Virus isolates differed by up to 17% and 11% at the nucleotide level for the partial S and L gene fragments, respectively, with less variation observed at the deduced amino acid level (10.5 and 2%, S and L, respectively). However, the Virus partial M gene fragment (which encodes the hypervariable mucin-like domain) of these Viruses differed by as much as 56% at the nucleotide level. Phylogenetic analysis of partial sequence differences suggests considerable mixing and movement of Ganjam Virus strains within India, with no clear relationship between genetic lineages and Virus geographic origin or year of isolation. Surprisingly, NSD Virus does not represent a distinct lineage, but appears as a variant with other Ganjam Virus among NSD Virus group.
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crimean congo hemorrhagic fever Virus encoded ovarian tumor protease activity is dispensable for Virus rna polymerase function
Journal of Virology, 2010Co-Authors: Eric Bergeron, Marina L. Khristova, Cesar G Albarino, Stuart T. NicholAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus (genus NairoVirus, family Bunyaviridae) associated with high case fatality disease outbreaks in regions of Africa, Europe, and Asia. The CCHFV genome consists of three negative-strand RNA segments, S, M, and L. The unusually large Virus L polymerase protein and the need for biosafety level 4 (BSL-4) containment conditions for work with infectious Virus have hampered the study of CCHFV replication. The L protein has an ovarian tumor (OTU) protease domain located in the N terminus, which has led to speculation that the protein may be autoproteolytically cleaved to generate the active Virus L polymerase and additional functions. We report the successful development of efficient CCHFV helper Virus-independent S, M, and L segment minigenome systems for analysis of Virus RNA and protein features involved in replication. The Virus RNA segment S, M, and L untranslated regions were found to be similar in support of replication of the respective minigenomes. In addition, the OTU domain located in the N terminus of the expressed Virus L protein was shown to be a functional protease. However, no evidence of L protein autoproteolytic processing was found, and the OTU protease activity was dispensable for Virus RNA replication. Finally, physiologically relevant doses of ribavirin inhibited CCHFV minigenome replication. These results demonstrated the utility of the minigenome system for use in BSL-2 laboratory settings to analyze CCHFV biology and in antiviral drug discovery programs for this important public health and bioterrorism threat.
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recent ancestry of kyasanur forest disease Virus
Emerging Infectious Diseases, 2009Co-Authors: Rajeev Mehla, Serena A Carroll, Prasanna N. Yergolkar, Pragya D. Yadav, Akhilesh C. Mishra, Bobbie R. Erickson, Stuart T. Nichol, Pradip V. Barde, Sandeep Kumar, Devendra T. MouryaAbstract:Kyasanur Forest disease Virus (KFDV) is a member of the mammalian Tick-Borne Virus group (previously referred to as the Tick-Borne encephalitis serogroup) of the family Flaviviridae and genus FlaviVirus (1). In addition to KFDV, this group contains Louping ill, Tick-Borne encephalitis, Omsk hemorrhagic fever, Langat, Powassan, Royal Farm, and Gadgets Gully Viruses. KFD was first recognized in 1957 in the Kyasanur Forest of Shimoga District, Karnataka State, India, when a disease causing a high number of deaths was observed in 2 species of monkeys: the black-faced langur (Semnopithecus entellus, earlier known as Presbytis entellus) and the red-faced bonnet monkey (Macaca radiata). Human cases were also found among persons who visited forests to collect firewood, grass, and other forest products. Human disease is characterized by an incubation period of ≈3–8 days, followed by chills, frontal headache, body ache, and high fever for 5–12 days, and a case-fatality rate >30% (2). During infection by KFDV, Virus titer remains high <10 days after onset of symptoms, as reported by Bhat et al. (3). However, Upadhyaya et al. (4) found that viremia in patients lasted for 12–13 days of illness and unlike most other flaviViruses, remains high during the first 3–6 days with titers as high as 3.1 × 106 PFU/mL. Continuing deaths in monkeys and an average of 400–500 human cases have been seen annually over the past 5 decades, commonly occurring in evergreen, semi-evergreen, and neighboring, moist, deciduous forest areas. An array of tick species, mainly Haemaphysalis spinigera, act as vectors for KFDV (5). This species of tick is widely distributed in tropical evergreen and deciduous forests of southern and central India and Sri Lanka. KFDV has also been isolated from 7 other species of this genus and from Dermacentor and Ixodes ticks. This disease is transmitted by ticks among ground birds and small mammals such as the white-tailed rat, white-bellied rat, shrew, and bat. High titers of Virus can be obtained after experimental infection of black-napped hares, porcupines, flying squirrels, Malabar giant squirrels, three-striped squirrels, gerbils, mice, long-tailed tree mice, and shrews (2–9). Until 1971, KFDV was endemic to the Sagar, Sorab, and Shikaripur taluks (counties) of Shimoga District (Figure 1). By 1972, a new focus of Virus activity appeared in Sirsi Taluk, Uttara Kannada District. Many KFDV isolates were obtained from Karnataka during 1957–1972 and maintained in a repository at the National Institute of Virology (NIV) in Pune, India. However, the Virus was found to be highly infectious, as shown by numerous infections in field and laboratory personnel (2,10), which resulted in suspension of work with this Virus until an appropriate BioSafety Level-3 laboratory was built at NIV in 2004. In 2006, this laboratory isolated a Virus from a serum sample of a patient suspected of having KFD that was obtained from the Virus Diagnostic Laboratory in Shimoga. Figure 1 Areas of Karnataka State, India, known to be affected by Kyasanur Forest disease (dark gray shading). More recent studies have identified KFDV in Saudi Arabia and the People’s Republic of China (11,12). During 1994–1995, a Virus was isolated from hemorrhagic fever patients in the Makkah region of Saudi Arabia and identified as a KFDV variant, referred to as the Alkhurma variant or subgroup (11,13,14). The prototype strain of KFDV from Saudi Arabia (strain 1176, isolated in 1995) and the KFDV reference strain from India (P-9605, isolated in 1957) differ from each another by only 8% at the genome nucleotide level, despite their temporal (38 years) and geographic (≈4,000 km) separation. A Virus initially referred to as Nanjianyin Virus, isolated in 1989 from a febrile patient in Nanjian County in the Hengduan Mountain region of Yunnan Province in southwestern China, was recently identified as a strain of KFDV (12). However, it is unclear whether this KFDV 1989 isolate from China is an authentic Virus isolate because it is virtually identical at the nucleotide level with the 1957 reference strain from India (P-9605), despite their being isolated 32 years and almost 3,000 km apart. The P-9605 strain was distributed widely to arboVirus reference laboratories. Reference KFDV Virus was used as part of the analysis of serum samples from Yunnan Province (15,16). Results of molecular epidemiologic studies have suggested that Tick-Borne flaviViruses have evolved slowly while dispersing north and west across Asian and European forests during the past few millennia (17–19). This pattern is different from that of rapidly evolving mosquito-borne flaviViruses, many of which can be transported long distances by migratory birds, persons, animals, or mosquito eggs (19,20). We examined the diversity and evolution of KFDV and present data that indicated that KFDV isolates from India, Saudi Arabia, and China share a recent common ancestor, indicating long-range movement of this Tick-Borne flaviVirus. In addition, we also estimated the evolution rate of KFDV and compared it with that of mosquito-borne flaviViruses.
Eric Bergeron - One of the best experts on this subject based on the ideXlab platform.
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identification of a novel lineage of crimean congo haemorrhagic fever Virus in dromedary camels united arab emirates
Journal of General Virology, 2021Co-Authors: Abdelmalik I Khalafalla, Eric Bergeron, Anna Uehara, Nasareldien A Hussein, Jing Zhang, Ying Tao, Ibrahim H Ibrahim, Mohamed Al A Hosani, Mohd F YusofAbstract:Crimean-Congo haemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The Virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.
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single dose replicon particle vaccine provides complete protection against crimean congo hemorrhagic fever Virus in mice
Emerging microbes & infections, 2019Co-Authors: Florine E M Scholte, Scott D Pegan, Stuart T. Nichol, Jessica R Spengler, Stephen R Welch, Jessica R. Harmon, Brendan T. Freitas, Markus H. Kainulainen, Joann D Colemanmccray, Eric BergeronAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is an emerging Tick-Borne Virus from the family Nairoviridae that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution,...
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rig i mediates an antiviral response to crimean congo hemorrhagic fever Virus
Journal of Virology, 2015Co-Authors: Jessica R Spengler, Jenish R Patel, Ayan K Chakrabarti, Marko Zivcec, Adolfo Garciasastre, Christina F Spiropoulou, Eric BergeronAbstract:ABSTRACT In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA Viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever Virus (CCHFV), a negative-sense RNA Virus with a 5′-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. IMPORTANCE CCHFV is a Tick-Borne Virus with a significant public health impact. In order for cells to respond to Virus infection, they must recognize the Virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential Viruses recognized by RIG-I.
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structure function and evolution of the crimean congo hemorrhagic fever Virus nucleocapsid protein
Journal of Virology, 2012Co-Authors: Stephen D Carter, Stuart T. Nichol, Rebecca Surtees, Thomas A. Edwards, Eric Bergeron, Cheryl T Walter, Antonio Ariza, Julian A Hiscox, John N. BarrAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is an emerging Tick-Borne Virus of the Bunyaviridae family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 A. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that of the recently reported N protein from strain YL04057 shows a close correspondence of all folds but significant transposition of the arm through a rotation of 180 degrees and a translation of 40 A. These observations suggest a structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding and oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally critical residues within these domains were identified using a minigenome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif; however, the cleaved N protein remains an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyaVirus but the arenaVirus Lassa Virus instead, suggesting that current segmented negative-strand RNA Virus taxonomy may need revision.
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crimean congo hemorrhagic fever Virus encoded ovarian tumor protease activity is dispensable for Virus rna polymerase function
Journal of Virology, 2010Co-Authors: Eric Bergeron, Marina L. Khristova, Cesar G Albarino, Stuart T. NicholAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus (genus NairoVirus, family Bunyaviridae) associated with high case fatality disease outbreaks in regions of Africa, Europe, and Asia. The CCHFV genome consists of three negative-strand RNA segments, S, M, and L. The unusually large Virus L polymerase protein and the need for biosafety level 4 (BSL-4) containment conditions for work with infectious Virus have hampered the study of CCHFV replication. The L protein has an ovarian tumor (OTU) protease domain located in the N terminus, which has led to speculation that the protein may be autoproteolytically cleaved to generate the active Virus L polymerase and additional functions. We report the successful development of efficient CCHFV helper Virus-independent S, M, and L segment minigenome systems for analysis of Virus RNA and protein features involved in replication. The Virus RNA segment S, M, and L untranslated regions were found to be similar in support of replication of the respective minigenomes. In addition, the OTU domain located in the N terminus of the expressed Virus L protein was shown to be a functional protease. However, no evidence of L protein autoproteolytic processing was found, and the OTU protease activity was dispensable for Virus RNA replication. Finally, physiologically relevant doses of ribavirin inhibited CCHFV minigenome replication. These results demonstrated the utility of the minigenome system for use in BSL-2 laboratory settings to analyze CCHFV biology and in antiviral drug discovery programs for this important public health and bioterrorism threat.
Aykut Ozdarendeli - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the cell culture based and the mouse brain derived inactivated vaccines against crimean congo hemorrhagic fever Virus in transiently immune suppressed is mouse model
PLOS Neglected Tropical Diseases, 2020Co-Authors: Shaikh Terkis Islam Pavel, Ahmet Kalkan, Hazel Yetiskin, Aykut OzdarendeliAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus in the Nairoviridae family within the Bunyavirales order of Viruses. Crimean-Congo hemorrhagic fever (CCHF) is the most widespread among Tick-Borne human viral diseases. It is endemic in many areas of Africa, Asia, the Middle East, in the Balkans, Russia and countries of the former Soviet Union. The confirmed CCHF cases were seen in Spain in 2016 to signify expansion of the Virus into new geographical areas. CCHFV causes a viral human disease characterized by sudden onset of fever, headache, abdominal pain, nausea, hypotension, hemorrhage, and hepatic dysfunction with fatality rates up to 30%. Currently, there are no spesific treatments or licensed vaccines available for CCHFV. The absence of a susceptible animal model for CCHFV infection was severely hindered work on the development of vaccines. However, several animal models of CCHFV infection have been recently developed and used to assess vaccine efficacy. In this study, we have used the transiently immune-suppressed (IS) mouse model that MAb-5A3 was used to block IFN-I signaling in immune intact, wild-type mice at the time of CCHFV infection to evaluate the immune response and efficacy of the cell culture based and the mouse brain derived inactivated vaccines against CCHFV. Both vaccine preparations have provided complete protection but the cell culture based vaccine more effectively induced to CCFHV spesific antibodies and T cell responses. This is the first comparison of the cell culture based and the mouse brain derived vaccines for assessing the protective efficacy and the immunogenicity in the IS mouse CCHFV model.
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Pseudo-plaque reduction neutralization test (PPRNT) for the measurement of neutralizing antibodies to Crimean-Congo hemorrhagic fever Virus
Virology journal, 2013Co-Authors: Nurettin Canakoglu, Sukru Tonbak, Munir Aktas, Yusuf Bolat, Ahmet Kalkan, Engin Berber, Mustafa Ertek, Mustafa D. Yoruk, Aykut OzdarendeliAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus of the genus NairoVirus family Bunyaviridae, which are enveloped Viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT) based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. Sixty-nine human serum samples (20 acute and 49 convalescent) were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT) to measure of CCHFV-neutralizing antibodies. Pseudo-plaque reduction neutralization test showed a high sensitivity (98%), specificity (100%) and agreement (96,6%) in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92). The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive method for the measurement of CCHF neutralizing antibodies. This novel assay could serve as useful tools for CCHF research in epidemiology, vaccine development and other studies of immunity. It also provides an alternative to PRNT when Viruses with no or poor CPE in cell culture.
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crimean congo hemorrhagic fever Virus genetic analysis and tick survey in turkey
Journal of Clinical Microbiology, 2006Co-Authors: Sukru Tonbak, Munir Aktas, Yusuf Bolat, Ahmet Kalkan, Kursat Altay, Ahmet Kursat Azkur, Nazir Dumanli, Aykut OzdarendeliAbstract:Crimean-Congo hemorrhagic fever Virus (CCHFV) is a Tick-Borne Virus in the family Bunyaviridae, genus NairoVirus. The Virus is transmitted to humans through infected tick bites or from direct contact with viremic animals or humans. In the present study, a total of 1,015 adult ticks were collected from cattle (603 specimens), sheep (17 specimens), and goats (395 specimens) in the Kelkit Valley in Turkey. Four tick species were recognized on the animals in the surveyed region. The most abundant species were Rhipicephalus bursa and Hyalomma marginatum marginatum, at 47.68% (484/1,015) and 46.40% (471/1,015), respectively. Reverse transcriptase PCR was used to recover partial sequences of the CCHFV small (S) genome segment. The presence of CCHFV was determined in 3 of 33 (9.09%) R. bursa pools and in 1 of 31 (3.22%) H. m. marginatum pools. Virus sequences from R. bursa were extremely different from those of the Greek CCHFV strain (U04958) isolated from an R. bursa tick. Phylogenetic analysis indicated that the CCHFV isolates obtained in this study clustered in group 5, whose range encompasses southwestern Russian and Kosovo. This is the first evidence of CCHFV in ticks from Turkey. Even though Hyalomma is the main vector for CCHFV, R. bursa may play a role in CCHFV transmission.