The Experts below are selected from a list of 55527 Experts worldwide ranked by ideXlab platform
Jerry Phelps - One of the best experts on this subject based on the ideXlab platform.
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Headliners: Liver Cancer: Hepatitis B Virus Mutation Predicts Liver Cancer.
Environmental Health Perspectives, 2004Co-Authors: Jerry PhelpsAbstract:Kuang SY, Jackson PE, Wang JB, Lu PX, Munoz A, Qian GS, Kensler TW, Groopman JD. 2004. Specific Mutations of hepatitis B Virus in plasma predict liver cancer development. Proc Natl Acad Sci USA 101:3575–3580. Liver cancer is the fifth most prevalent form of cancer worldwide, causing more than 500,000 deaths annually, according to the World Health Organization. Exposure to the hepatitis B Virus (HBV) is a major risk factor in the development of liver cancer. Now a team including NIEHS grantees Alvaro Munoz, John D. Groopman, and Thomas W. Kensler, all of the Johns Hopkins Bloomberg School of Public Health, has identified a biomarker that may predict future cases of liver cancer in HBV carriers. Previous work by members of this team has shown that HBV exposure causes a 7-fold increase in risk. Exposure to aflatoxin, a mold product commonly found in peanuts and grains, increases the risk of liver cancer by 3.5 times. Combined exposure to these two agents results in a remarkable 60-fold increase in the risk of developing liver cancer. This is an especially troubling public health problem in China, where HBV and aflatoxin exposures are both very high. In the current study, the researchers examined the prevalence a particular HBV Mutation in the plasma and tumors of liver cancer patients living in Qidong, China. Initial studies determined that about three-fourths of the tumors from an initial group of 70 patients contained the Mutation. In a second group of 15 liver cancer patients chosen from a cohort of high-risk individuals, the investigators determined that about half had detectable levels of the HBV Mutation in their blood several years before the cancer appeared. These findings suggest that detection of the mutated HBV in the blood is an early warning sign of subsequent liver cancer development, and suggest its use as an intermediate end point in prevention and intervention trials. –Jerry Phelps
Calla Martyn - One of the best experts on this subject based on the ideXlab platform.
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two sides of a coin a zika Virus Mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors
Journal of Virology, 2020Co-Authors: Danilo Lemos, Jackson B Stuart, William Louie, Anil Singapuri, Ana L Ramirez, Jennifer Watanabe, Jodie Usachenko, Rebekah I Keesler, Claudia Sanchez San Martin, Calla MartynAbstract:Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika Virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intrahost substitution, M1404I, in the ZIKV polyprotein, located in nonstructural protein 2B (NS2B). Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at a subconsensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I has occurred rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, Mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases viral fitness in nonpregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to that of ZIKV M1404, we observed that ZIKV I1404 produced lower viremias in nonpregnant macaques and was a weaker competitor in tissues. In pregnant wild-type mice, ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, in contrast to ZIKV M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Aedes aegypti mosquitoes transmitted ZIKV I1404 more poorly than ZIKV M1404. Our data highlight the complexity of arboVirus Mutation-fitness dynamics and suggest that intrahost ZIKV Mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics.IMPORTANCE Although Zika Virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a Mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the Mutation and fetal death, we performed additional studies with ZIKV with the Mutation in nonpregnant macaques, pregnant mice, and mosquitoes. We observed that the Mutation increased the ability of the Virus to infect mouse fetuses but decreased its capacity to produce high levels of Virus in the blood of nonpregnant macaques and to be transmitted by mosquitoes. This study shows that Mutations in mosquito-borne Viruses like ZIKV that increase fitness in pregnant vertebrates may not spread in outbreaks when they compromise transmission via mosquitoes and fitness in nonpregnant hosts.
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two sides of a coin a zika Virus Mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors
bioRxiv, 2020Co-Authors: Danilo Lemos, Jackson B Stuart, William Louie, Anil Singapuri, Ana L Ramirez, Jennifer Watanabe, Jodie Usachenko, Rebekah I Keesler, Claudia Sanchez San Martin, Calla MartynAbstract:Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika Virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intra-host Mutation, M1404I, in the ZIKV polyprotein, located in NS2B. Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at sub-consensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I occurs rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, Mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases fitness in non-pregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to M1404, we observed that I1404 produced lower viremias in non-pregnant macaques and was a weaker competitor in tissues. In pregnant wildtype mice ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, contrasting with M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Ae. aegypti transmitted ZIKV I1404 more poorly than M1404. Our data highlight the complexity of arboVirus Mutation-fitness dynamics, and suggest that intrahost ZIKV Mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics.
Carlos F Barbas - One of the best experts on this subject based on the ideXlab platform.
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a chemically programmed antibody is a long lasting and potent inhibitor of influenza neuraminidase
ChemBioChem, 2012Co-Authors: Masahiko Hayakawa, Narihiro Toda, Nancy Carrillo, Natalie J Thornburg, James E Crowe, Carlos F BarbasAbstract:Globalization makes reoccurring influenza pandemics a probable health care concern for the foreseeable future.[1] Although vaccination plays a primary role in the prevention of influenza epidemics and pandemics, vaccines must be designed and produced in advance of the influenza season and cannot be supplied on-demand in response to Virus Mutation.[2] Thus, efficient anti-influenza drugs are as important as vaccination in epidemic management.[3] Currently, the neuraminidase inhibitors zanamivir (1)[4] and oseltamivir (2)[5] are the mainstay drugs for treatment of infected patients (Figure 1). Each must be administered twice-daily due to their rapid excretion from the body. Therefore, long-lasting and potent anti-influenza drugs are highly attractive alternatives for treatment of influenza infection as well as for prophylaxis.[6]
Danilo Lemos - One of the best experts on this subject based on the ideXlab platform.
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two sides of a coin a zika Virus Mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors
Journal of Virology, 2020Co-Authors: Danilo Lemos, Jackson B Stuart, William Louie, Anil Singapuri, Ana L Ramirez, Jennifer Watanabe, Jodie Usachenko, Rebekah I Keesler, Claudia Sanchez San Martin, Calla MartynAbstract:Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika Virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intrahost substitution, M1404I, in the ZIKV polyprotein, located in nonstructural protein 2B (NS2B). Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at a subconsensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I has occurred rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, Mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases viral fitness in nonpregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to that of ZIKV M1404, we observed that ZIKV I1404 produced lower viremias in nonpregnant macaques and was a weaker competitor in tissues. In pregnant wild-type mice, ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, in contrast to ZIKV M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Aedes aegypti mosquitoes transmitted ZIKV I1404 more poorly than ZIKV M1404. Our data highlight the complexity of arboVirus Mutation-fitness dynamics and suggest that intrahost ZIKV Mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics.IMPORTANCE Although Zika Virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a Mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the Mutation and fetal death, we performed additional studies with ZIKV with the Mutation in nonpregnant macaques, pregnant mice, and mosquitoes. We observed that the Mutation increased the ability of the Virus to infect mouse fetuses but decreased its capacity to produce high levels of Virus in the blood of nonpregnant macaques and to be transmitted by mosquitoes. This study shows that Mutations in mosquito-borne Viruses like ZIKV that increase fitness in pregnant vertebrates may not spread in outbreaks when they compromise transmission via mosquitoes and fitness in nonpregnant hosts.
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two sides of a coin a zika Virus Mutation selected in pregnant rhesus macaques promotes fetal infection in mice but at a cost of reduced fitness in nonpregnant macaques and diminished transmissibility by vectors
bioRxiv, 2020Co-Authors: Danilo Lemos, Jackson B Stuart, William Louie, Anil Singapuri, Ana L Ramirez, Jennifer Watanabe, Jodie Usachenko, Rebekah I Keesler, Claudia Sanchez San Martin, Calla MartynAbstract:Although fetal death is now understood to be a severe outcome of congenital Zika syndrome, the role of viral genetics is still unclear. We sequenced Zika Virus (ZIKV) from a rhesus macaque fetus that died after inoculation and identified a single intra-host Mutation, M1404I, in the ZIKV polyprotein, located in NS2B. Targeted sequencing flanking position 1404 in 9 additional macaque mothers and their fetuses identified M1404I at sub-consensus frequency in the majority (5 of 9, 56%) of animals and some of their fetuses. Despite its repeated presence in pregnant macaques, M1404I occurs rarely in humans since 2015. Since the primary ZIKV transmission cycle is human-mosquito-human, Mutations in one host must be retained in the alternate host to be perpetuated. We hypothesized that ZIKV I1404 increases fitness in non-pregnant macaques and pregnant mice but is less efficiently transmitted by vectors, explaining its low frequency in humans during outbreaks. By examining competitive fitness relative to M1404, we observed that I1404 produced lower viremias in non-pregnant macaques and was a weaker competitor in tissues. In pregnant wildtype mice ZIKV I1404 increased the magnitude and rate of placental infection and conferred fetal infection, contrasting with M1404, which was not detected in fetuses. Although infection and dissemination rates were not different, Ae. aegypti transmitted ZIKV I1404 more poorly than M1404. Our data highlight the complexity of arboVirus Mutation-fitness dynamics, and suggest that intrahost ZIKV Mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics.
Althea S Hayden - One of the best experts on this subject based on the ideXlab platform.
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whole genome sequencing of measles Virus genotypes h1 and d8 during outbreaks of infection following the 2010 olympic winter games reveals viral transmission routes
The Journal of Infectious Diseases, 2015Co-Authors: Jennifer L Gardy, Monika Naus, Ashraf Amlani, Walter Chung, Alberto Severini, Mel Krajden, David Puddicombe, Vanita Sahni, Althea S HaydenAbstract:: We used whole-genome sequencing to investigate a dual-genotype outbreak of measles occurring after the XXI Olympic Winter Games in Vancouver, Canada. By sequencing 27 complete genomes from H1 and D8 genotype measles Viruses isolated from outbreak cases, we estimated the Virus Mutation rate, determined that person-to-person transmission is typically associated with 0 Mutations between isolates, and established that a single introduction of H1 Virus led to the expansion of the outbreak beyond Vancouver. This is the largest measles genomics project to date, revealing novel aspects of measles Virus genetics and providing new insights into transmission of this reemerging viral pathogen.
