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Full-Text Articles in Virology

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman Jul 2019

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …


Molecular Evolution Of Dengue Type 2 Virus In Thailand, Rebeca Rico-Hesse, Lisa M. Harrison, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis Nov 2017

Molecular Evolution Of Dengue Type 2 Virus In Thailand, Rebeca Rico-Hesse, Lisa M. Harrison, Ananda Nisalak, David W. Vaughn, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis

Sharone Green

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained …


The Ifitms Inhibit Zika Virus Replication, George Savidis, Jill Perreira, Jocelyn M. Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L. Brass Jun 2016

The Ifitms Inhibit Zika Virus Replication, George Savidis, Jill Perreira, Jocelyn M. Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L. Brass

Sharone Green

Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.


A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon Jan 2016

A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon

Celia A. Schiffer

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, …


Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg Jun 2015

Positive Selection Drives Preferred Segment Combinations During Influenza Virus Reassortment, Konstantin Zeldovich, Ping Liu, Nicholas Renzette, Matthieu Foll, Serena Pham, Sergey Venev, Glen Gallagher, Daniel Bolon, Evelyn Kurt-Jones, Jeffrey Jensen, Daniel Caffrey, Celia Schiffer, Timothy Kowalik, Jennifer Wang, Robert Finberg

Celia A. Schiffer

Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 …


A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello Dec 2014

A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello

Neal Silverman

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells …


Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer Nov 2011

Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer

Celia A. Schiffer

The current effectiveness of HAART in the management of HIV infection is compromised by the emergence of extensively cross-resistant strains of HIV-1, requiring a significant need for new therapeutic agents. Due to its crucial role in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1 protease continues to be a major development target for antiretroviral therapy. However, new protease inhibitors must have higher thresholds to the development of resistance and cross-resistance. Research has demonstrated that the binding characteristics between a protease inhibitor and the active site of the HIV-1 protease are key factors in the development of resistance. More …