The Experts below are selected from a list of 68439 Experts worldwide ranked by ideXlab platform
Johanna S. Salzer - One of the best experts on this subject based on the ideXlab platform.
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The Pox in the North American Backyard: Volepox Virus Pathogenesis in California Mice (Peromyscus californicus)
2015Co-Authors: Nadia F. Gallardo-romero, Clifton P. Drew, Sonja L. Weiss, Maureen G. Metcalfe, Yoshinori J. Nakazawa, Scott K. Smith, Ginny L. Emerson, Christina L. Hutson, Johanna S. Salzer, Jeanine H. BartlettAbstract:Volepox Virus (VPXV) was first isolated in 1985 from a hind foot scab of an otherwise healthy California vole (Microtus californicus). Subsequent surveys in San Mateo County, CA, revealed serological evidence suggesting that VPXV is endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus truei) was collected in 1988. Since then, few studies have been conducted regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence and role as a potential zoonotic agent remain unknown. To increase our understanding of VPXV disease progression, we challenged 24 California mice (Peromyscus californicus) intranasally with 1.66103 PFU of purified VPXV. By day five post infection (pi) we observed decreased activity level, conjunctivitis, ruffled hair, skin lesions, facial edema, and crusty noses. A mortality rate of 54 % was noted by day eight pi. In addition, internal organ necrosis and hemorrhages were observed during necropsy of deceased or euthanized animals. Viral loads in tissues (brain, gonad, kidney, liver, lung, spleen, submandibular lymph node, and adrenal gland), bodily secretions (saliva, and tears), and excretions (urine, and/or feces) were evaluated and compared using real time-PCR and tissue culture. Viral loads measured as high as 26109 PFU/mL in some organs. Our results sugges
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the pox in the north american backyard volepox Virus Pathogenesis in california mice peromyscus californicus
PLOS ONE, 2012Co-Authors: Nadia Gallardoromero, Clifton P. Drew, Maureen G. Metcalfe, Yoshinori J. Nakazawa, Scott K. Smith, Ginny L. Emerson, Christina L. Hutson, Johanna S. Salzer, Sonja WeissAbstract:Volepox Virus (VPXV) was first isolated in 1985 from a hind foot scab of an otherwise healthy California vole (Microtus californicus). Subsequent surveys in San Mateo County, CA, revealed serological evidence suggesting that VPXV is endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus truei) was collected in 1988. Since then, few studies have been conducted regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence and role as a potential zoonotic agent remain unknown. To increase our understanding of VPXV disease progression, we challenged 24 California mice (Peromyscus californicus) intranasally with 1.6×103 PFU of purified VPXV. By day five post infection (pi) we observed decreased activity level, conjunctivitis, ruffled hair, skin lesions, facial edema, and crusty noses. A mortality rate of 54% was noted by day eight pi. In addition, internal organ necrosis and hemorrhages were observed during necropsy of deceased or euthanized animals. Viral loads in tissues (brain, gonad, kidney, liver, lung, spleen, submandibular lymph node, and adrenal gland), bodily secretions (saliva, and tears), and excretions (urine, and/or feces) were evaluated and compared using real time-PCR and tissue culture. Viral loads measured as high as 2×109 PFU/mL in some organs. Our results suggest that VPXV can cause extreme morbidity and mortality within rodent populations sympatric with the known VPXV reservoirs.
Michael S. Diamond - One of the best experts on this subject based on the ideXlab platform.
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Zika Virus Pathogenesis and Tissue Tropism
Cell host & microbe, 2017Co-Authors: Jerome James Miner, Michael S. DiamondAbstract:Although Zika Virus (ZIKV) was isolated approximately 70 years ago, few experimental studies had been published prior to 2016. The recent spread of ZIKV to countries in the Western Hemisphere is associated with reports of microcephaly, congenital malformations, and Guillain-Barre syndrome. This has resulted in ZIKV being declared a public health emergency and has greatly accelerated the pace of ZIKV research and discovery. Within a short time period, useful mouse and non-human primate disease models have been established, and pre-clinical evaluation of therapeutics and vaccines has begun. Unexpectedly, ZIKV exhibits a broad tropism and persistence in body tissues and fluids, which contributes to the clinical manifestations and epidemiology that have been observed during the current epidemic. In this Review, we highlight recent advances in our understanding of ZIKV Pathogenesis, tissue tropism, and the resulting pathology and discuss areas for future investigation.
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a mouse model of zika Virus Pathogenesis
Cell Host & Microbe, 2016Co-Authors: Helen M Lazear, Jerome James Miner, Derek J Platt, Amber M Smith, Estefania Fernandez, Jennifer Govero, Michael S. DiamondAbstract:Summary The ongoing Zika Virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barre syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and Pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3 −/− Irf5 −/− Irf7 −/− triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor ( Ifnar1 −/− ) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3 −/− , Irf5 −/− , and Mavs −/− knockout mice exhibited no overt illness. Ifnar1 −/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1 −/− mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV Pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease Pathogenesis.
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molecular insight into dengue Virus Pathogenesis and its implications for disease control
Cell, 2015Co-Authors: Michael S. Diamond, Theodore C PiersonAbstract:Dengue Virus (DENV) is a mosquito-transmitted RNA Virus that infects an estimated 390 million humans each year. Here, we review recent advances in our understanding of the biology of DENV and describe knowledge gaps that have impacted the development of effective vaccines and therapeutics.
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west nile Virus infection and immunity
Nature Reviews Microbiology, 2013Co-Authors: Michael S. Diamond, Mehul S Suthar, Michael GaleAbstract:Here, Suthar, Diamond and Gale review recent insights into West Nile Virus Pathogenesis and the host immune responses that this Virus activates. Given the continuing spread of the Virus in the Western hemisphere, a better understanding of these host–Virus interactions is crucial and should facilitate the development of effective vaccines and therapeutics. West Nile Virus (WNV) is an emerging neurotropic flaviVirus that is transmitted to humans through the bite of an infected mosquito. WNV has disseminated broadly in the Western hemisphere and now poses a significant public health risk. The continuing spread of WNV, combined with the lack of specific therapeutics or vaccines to combat or prevent infection, imparts a pressing need to identify the viral and host processes that control the outcome of and immunity to WNV infection. Here, we provide an overview of recent research that has revealed the Virus–host interface controlling WNV infection and immunity.
Ann M. Arvin - One of the best experts on this subject based on the ideXlab platform.
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Age-Associated Differences in Infection of Human Skin in the SCID Mouse Model of Varicella-Zoster Virus Pathogenesis
Journal of virology, 2018Co-Authors: Leigh Zerboni, Phillip Sung, Gordon K. Lee, Ann M. ArvinAbstract:Varicella-zoster Virus (VZV) is the skin-tropic human alphaherpesVirus responsible for both varicella-zoster and herpes zoster. Varicella-zoster and herpes zoster skin lesions have similar morphologies, but herpes zoster occurs disproportionally in older individuals and is often associated with a more extensive local rash and severe zoster-related neuralgia. We hypothesized that skin aging could also influence the outcome of the anterograde axonal transport of VZV to skin. We utilized human skin xenografts maintained in immunodeficient (SCID) mice to study VZV-induced skin pathology in vivo in fetal and adult skin xenografts. Here we found that VZV replication is enhanced in skin from older compared to younger adults, correlating with clinical observations. In addition to measures of VZV infection, we examined the expression of type I interferon (IFN) pathway components in adult skin and investigated elements of the cutaneous proliferative and inflammatory response to VZV infection in vivo Our results demonstrated that VZV infection of adult skin triggers intrinsic IFN-mediated responses such as we have described in VZV-infected fetal skin xenografts, including MxA as well as promyelocytic leukemia protein (PML), in skin cells surrounding lesions. Further, we observed that VZV elicited altered cell signaling and proliferative and inflammatory responses that are involved in wound healing, driven by follicular stem cells. These cellular changes are consistent with VZV-induced activation of STAT3 and suggest that VZV exploits the wound healing process to ensure efficient delivery of the Virus to keratinocytes. Adult skin xenografts offer an approach to further investigate VZV-induced skin pathologies in vivoIMPORTANCE Varicella-zoster Virus (VZV) is the agent responsible for both varicella-zoster and herpes zoster. Herpes zoster occurs disproportionally in older individuals and is often associated with a more extensive local rash and severe zoster-related neuralgia. To examine the effect of skin aging on VZV skin lesions, we utilized fetal and adult human skin xenografts maintained in immunodeficient (SCID) mice. We measured VZV-induced skin pathology, examined the expression of type I interferon (IFN) pathway components in adult skin, and investigated elements of the cutaneous proliferative and inflammatory response to VZV infection in vivo Our results demonstrate that characteristics of aging skin are preserved in xenografts; that VZV replication is enhanced in skin from older compared to younger adults, correlating with clinical observations; and that VZV infection elicits altered cell signaling and inflammatory responses. Adult skin xenografts offer an approach to further investigate VZV-induced skin pathologies in vivo.
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molecular mechanisms of varicella zoster Virus Pathogenesis
Nature Reviews Microbiology, 2014Co-Authors: Leigh Zerboni, Nandini Sen, Stefan L Oliver, Ann M. ArvinAbstract:Varicella zoster Virus (VZV) is the causative agent of varicella (chickenpox) and zoster (shingles). Investigating VZV Pathogenesis is challenging as VZV is a human-specific Virus and infection does not occur, or is highly restricted, in other species. However, the use of human tissue xenografts in mice with severe combined immunodeficiency (SCID) enables the analysis of VZV infection in differentiated human cells in their typical tissue microenvironment. Xenografts of human skin, dorsal root ganglia or foetal thymus that contains T cells can be infected with mutant Viruses or in the presence of inhibitors of viral or cellular functions to assess the molecular mechanisms of VZV-host interactions. In this Review, we discuss how these models have improved our understanding of VZV Pathogenesis.
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Disruption of PML Nuclear Bodies Is Mediated by ORF61 SUMO-Interacting Motifs and Required for Varicella- Zoster Virus Pathogenesis in Skin
2013Co-Authors: Li Wang, Stefan L Oliver, Marvin Sommer, Jaya Rajamani, Mike Reichelt, Ann M. ArvinAbstract:Promyelocytic leukemia protein (PML) has antiviral functions and many Viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral Pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infected cells in vivo. Varicella-zoster Virus (VZV) is a human alphaherpesVirus that causes cutaneous lesions during primary and recurrent infection. Here we show that VZV disrupts PML NBs in infected cells in human skin xenografts in SCID mice and that the disruption is achieved by open reading frame 61 (ORF61) protein via its SUMO-interacting motifs (SIMs). Three conserved SIMs mediated ORF61 binding to SUMO1 and were required for ORF61 association with and disruption of PML NBs. Mutation of the ORF61 SIMs in the VZV genome showed that these motifs were necessary for PML NB dispersal in VZV-infected cells in vitro. In vivo, PML NBs were highly abundant, especially in basal layer cells of uninfected skin, whereas their frequency was significantly decreased in VZV-infected cells. In contrast, mutation of the ORF61 SIMs reduced ORF61 association with PML NBs, most PML NBs remained intact and importantly, viral replication in skin was severely impaired. The ORF61 SIM mutant Virus failed to cause the typical VZV lesions that penetrate across the basement membrane into the dermis and viral spread in the epidermis was limited. These experiments indicate that VZV Pathogenesis in skin depends upon the ORF61-mediated disruption of PML NBs and that the ORF61 SUMO-binding function is necessary for this effect. More broadly, our study elucidates th
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Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and required for varicella-zoster Virus Pathogenesis in skin.
Public Library of Science (PLoS), 2011Co-Authors: Li Wang, Stefan L Oliver, Marvin Sommer, Jaya Rajamani, Mike Reichelt, Ann M. ArvinAbstract:Promyelocytic leukemia protein (PML) has antiviral functions and many Viruses encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence of the relevance of PML NB modification for viral Pathogenesis is limited and little is known about viral gene functions required for PML NB disruption in infected cells in vivo. Varicella-zoster Virus (VZV) is a human alphaherpesVirus that causes cutaneous lesions during primary and recurrent infection. Here we show that VZV disrupts PML NBs in infected cells in human skin xenografts in SCID mice and that the disruption is achieved by open reading frame 61 (ORF61) protein via its SUMO-interacting motifs (SIMs). Three conserved SIMs mediated ORF61 binding to SUMO1 and were required for ORF61 association with and disruption of PML NBs. Mutation of the ORF61 SIMs in the VZV genome showed that these motifs were necessary for PML NB dispersal in VZV-infected cells in vitro. In vivo, PML NBs were highly abundant, especially in basal layer cells of uninfected skin, whereas their frequency was significantly decreased in VZV-infected cells. In contrast, mutation of the ORF61 SIMs reduced ORF61 association with PML NBs, most PML NBs remained intact and importantly, viral replication in skin was severely impaired. The ORF61 SIM mutant Virus failed to cause the typical VZV lesions that penetrate across the basement membrane into the dermis and viral spread in the epidermis was limited. These experiments indicate that VZV Pathogenesis in skin depends upon the ORF61-mediated disruption of PML NBs and that the ORF61 SUMO-binding function is necessary for this effect. More broadly, our study elucidates the importance of PML NBs for the innate control of a viral pathogen during infection of differentiated cells within their tissue microenvironment in vivo and the requirement for a viral protein with SUMO-binding capacity to counteract this intrinsic barrier
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varicella zoster Virus Pathogenesis and immunobiology new concepts emerging from investigations with the scidhu mouse model
Journal of Virology, 2005Co-Authors: Jaya Besser, Allison Abendroth, Charles Grose, Ann M. ArvinAbstract:Varicella-zoster Virus (VZV) is an alphaherpesVirus with a genome of ∼125,000 bp encoding at least 70 unique open reading frames (ORFs) (3, 9, 10, 15). Primary VZV infection is associated with a cell-associated viremia and a diffuse cutaneous rash recognized as varicella, or chickenpox. VZV appears to cause viremia by infecting lymphocytes. VZV establishes latency in sensory ganglia and causes herpes zoster upon reactivation. VZV is sustained in the human population, which is its only natural reservoir, primarily by direct contact with infectious Virus in varicella or zoster skin lesions or in respiratory secretions. Investigating the molecular mechanisms of VZV Pathogenesis has been difficult because of VZV's restricted infectivity for nonhuman species in vivo and the highly cell-associated nature of VZV replication in vitro. These obstacles have been addressed by the development of the SCIDhu mouse model to examine VZV Pathogenesis and immunobiology in vivo (5-7, 19, 30-34, 37, 40-42) and by the making of genetically altered VZV recombinants from VZV cosmids (11, 20, 28). Cosmid mutagenesis can be useful to define essential regions of the VZV genome if infectious Virus cannot be recovered without genetic complementation. When genetic changes are not lethal, VZV mutants can be evaluated in vitro and in human T-cell and skin xenografts in SCID mice to determine how particular VZV gene products contribute to virulence in differentiated human cells within their unique tissue microenvironments in vivo. The purpose of this review is to highlight new insights about VZV Pathogenesis and immunobiology that have emerged from analyses of VZV infection in the SCIDhu mouse model and from examination of the differential effects of mutations targeting ORF47, which encodes a viral kinase/tegument protein, on VZV tropism for skin and T cells. Clinical observations indicate that primary VZV infection begins with respiratory mucosal inoculation and that the characteristic chickenpox rash develops after an incubation period of 10 to 21 days (3, 9). In the absence of experimental data, early events in VZV Pathogenesis have been compared to mousepox (16). According to this model, VZV is presumed to infect mononuclear cells in regional lymph nodes, causing a primary viremia that carries the Virus to reticuloendothelial organs, such as the liver, for a phase of viral amplification, which is followed by a secondary viremia in the late incubation period that results in VZV transport to skin. Instead, our recent experiments with the SCIDhu mouse model support the concept that infected T cells have the potential to mediate VZV transfer to skin immediately after entering the circulation during primary viremia and suggest that the prolonged interval between exposure and the appearance of varicella skin lesions reflects the time required for VZV to overcome previously unrecognized but potent innate immune barriers, especially alpha interferon (IFN-α) production, mounted directly by epidermal cells in vivo (27). Experiments analyzing VZV recombinants with disrupted ORF47 protein kinase activity point to differences in the minimal requirements for cell fusion and virion formation in the Pathogenesis of VZV infection of skin and T cells in vivo (7). In a broader context, these observations about VZV Pathogenesis and immunobiology point to accommodations between VZV and the host that have allowed the Virus to persist in the human population so successfully. Virus-host interactions that ensure the gradual formation of cutaneous lesions containing infectious Virus at the skin surfaces should function to avoid an otherwise incapacitating infection of the host that would limit opportunities for VZV transmission to other susceptible individuals. New information about events in VZV Pathogenesis and differences in the genetic requirements for VZV replication in skin and T cells also suggest that the design of “second-generation” live attenuated varicella vaccines might focus on preserving infectivity in skin and blocking T cell tropism.
Robert E. Johnston - One of the best experts on this subject based on the ideXlab platform.
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role of alpha beta interferon in venezuelan equine encephalitis Virus Pathogenesis effect of an attenuating mutation in the 5 untranslated region
Journal of Virology, 2001Co-Authors: Laura J White, Jiagang Wang, Nancy L Davis, Robert E. JohnstonAbstract:Venezuelan equine encephalitis Virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5′ untranslated region (UTR) of the V3000 genome resulted in a Virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of Virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-α/β) activity in VEE Pathogenesis. In IFN-α/βR −/− mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-α/βR −/− mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant Virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-α/β pathway. In cells derived from IFN-α/βR −/− mice, the mutant Virus showed no growth disadvantage compared to the wild-type Virus, suggesting that IFN-α/β plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-α/β between V3000 and V3043, but the mutant Virus was more sensitive than V3000 to the antiviral actions of IFN-α/β in two separate in vitro assays, suggesting that the increased sensitivity to IFN-α/β plays a major role in the in vivo attenuation of V3043.
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role of dendritic cell targeting in venezuelan equine encephalitis Virus Pathogenesis
Journal of Virology, 2000Co-Authors: Gene H Macdonald, Robert E. JohnstonAbstract:The initial steps of Venezuelan equine encephalitis Virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which migrate to the draining lymph node following activation. A point mutation in the E2 glycoprotein gene of VEE that renders the Virus avirulent and compromises its ability to spread beyond the draining lymph blocked the appearance of virally infected dendritic cells in the lymph node in vivo. A second-site suppressor mutation that restores viral spread to lymphoid tissues and partially restore virulence likewise restored the ability of VEE to infect dendritic cells in vivo.
Jacqueline M Katz - One of the best experts on this subject based on the ideXlab platform.
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infection with highly pathogenic h7 influenza Viruses results in an attenuated proinflammatory cytokine and chemokine response early after infection
The Journal of Infectious Diseases, 2011Co-Authors: Jessica A Belser, Jacqueline M Katz, Hui Zeng, Terrence M. TumpeyAbstract:Avian influenza A Viruses of the H7 subtype have resulted in more than 100 cases of human infection since 2002. Highly pathogenic avian influenza (HPAI) H7 Viruses have the capacity to cause severe respiratory disease and even death; however, the induction of the human innate immune response to H7 Virus infection has not been well characterized. To better understand H7 Virus Pathogenesis in the human respiratory tract, we employed a polarized human bronchial epithelial cell model and primary human monocyte-derived macrophages. Here, we show that infection with HPAI H7 Viruses resulted in a delayed and weakened production of cytokines, including the type I interferon response, compared with infections of other influenza A subtypes, including H7 Viruses of low pathogenicity. These studies revealed that H7 Viruses vary greatly in their ability to activate host innate responses and may contribute to the virulence of these Viruses observed in humans.
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past present and possible future human infection with influenza Virus a subtype h7
Emerging Infectious Diseases, 2009Co-Authors: Jessica A Belser, Jacqueline M Katz, Carolyn B Bridges, Terrence M. TumpeyAbstract:Influenza A subtype H7 Viruses have resulted in >100 cases of human infection since 2002 in the Netherlands, Italy, Canada, the United States, and the United Kingdom. Clinical illness from subtype H7 infection ranges from conjunctivitis to mild upper respiratory illness to pneumonia. Although subtype H7 infections have resulted in a smaller proportion of hospitalizations and deaths in humans than those caused by subtype H5N1, some subtype H7 strains appear more adapted for human infection on the basis of their Virus-binding properties and illness rates among exposed persons. Moreover, increased isolation of subtype H7 influenza Viruses from poultry and the ability of this subtype to cause severe human disease underscore the need for continued surveillance and characterization of these Viruses. We review the history of human infection caused by subtype H7. In addition, we discuss recently identified molecular correlates of subtype H7 Virus Pathogenesis and assess current measures to prevent future subtype H7 Virus infection.
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Pathogenesis of emerging avian influenza Viruses in mammals and the host innate immune response
Immunological Reviews, 2008Co-Authors: Taronna R Maines, Terrence M. Tumpey, Jessica A Belser, Hui Zeng, Kristy J Szretter, Lucy A Perrone, Rick A Bright, Jacqueline M KatzAbstract:Summary: InfluenzaAVirusesofavianoriginrepresentanemergingthreatto human health as the progenitors of the next influenza pandemic. Inrecent years, highly pathogenic avian influenza H5N1 Viruses have causedunprecedented epizootics on three continents and rare but highly fataldisease among humans exposed to diseased birds. AvianViruses of the H7and H9 subtypes have also infected humans but generally resulted in farmilder disease, yet they too should be considered as possible pandemicthreats. Influenza Virus infection elicits a complex network of hostimmune responses that, in uncomplicated influenza, results in effectivecontrol of theVirus andthedevelopment oflong-termmemoryresponses.However, fatal avian H5N1 Virus infection in both humans and experi-mental mammalian models is characterized by a high viral load in therespiratory tract, peripheral leukopenia and lymphopenia, a massiveinfiltration of macrophages into the lung, and dysregulation of cytokineand chemokine responses. This review focuses on avian influenza Virusesas a pandemic threat, their induction of host innate immune responses inmammalian species, and the contribution of these responses to the diseaseprocess.Keywords: avian influenza Virus, Pathogenesis, innate immunity
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Molecular Correlates of Influenza A H5N1 Virus Pathogenesis in Mice
Journal of virology, 2000Co-Authors: Jacqueline M Katz, Terrence M. Tumpey, Catherine B. Smith, Michael Shaw, Kanta SubbaraoAbstract:Highly pathogenic avian influenza A H5N1 Viruses caused an outbreak of human respiratory illness in Hong Kong. Of 15 human H5N1 isolates characterized, nine displayed a high-, five a low-, and one an intermediate-pathogenicity phenotype in the BALB/c mouse model. Sequence analysis determined that five specific amino acids in four proteins correlated with pathogenicity in mice. Alone or in combination, these specific residues are the likely determinants of virulence of human H5N1 influenza Viruses in this model.
