interferon
Pathogenesis and ImmunityOutbreak Severity of Highly Pathogenic Avian Influenza A(H5N8) Viruses Is Inversely Correlated to Polymerase Complex Activity and Interferon InductionCompared to the 2014-15 outbreak, the 2016-17 outbreak of influenza A(H5N8) viruses in the Netherlands and Europe was more virulent; the number of dead or diseased wild birds found and the severity of pathological changes were higher during the 2016-17 outbreak. The polymerase complex plays an important role in influenza virus virulence, and the gene segments of influenza A(H5N8) viruses reassorted extensively between the outbreaks. In...
Virus-Cell InteractionsEpstein-Barr Virus (EBV) Tegument Protein BGLF2 Suppresses Type I Interferon Signaling To Promote EBV ReactivationType I interferons are important for controlling virus infection. We have found that the Epstein-Barr virus (EBV) BGLF2 tegument protein binds to a protein in the type I interferon signaling pathway Tyk2 and inhibits the expression of genes induced by type I interferons. Treatment of EBV-infected cells with type I interferon inhibits reactivation of the virus, while expression of EBV BGLF2 reduces the ability of type I interferon to...
Cellular Response to InfectionRelative Contributions of the cGAS-STING and TLR3 Signaling Pathways to Attenuation of Herpes Simplex Virus 1 ReplicationThe magnitude of fatal infections caused by all different viruses in human and animal populations justifies a better understanding of the host innate immune response process that attenuates virus replication. In particular, the relative contributions of different signaling pathways which are responsible for the generation of the innate immune response are still largely unknown. In this study, we used STING-noninteracting TRIF mutants to...
Virus-Cell InteractionsVesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral StateInterferons are important antiviral cytokines that work by inducing hundreds of host genes whose products inhibit the replication of many viruses. While the antiviral activity of interferon has long been known, the identities and mechanisms of action of most interferon-induced antiviral proteins remain to be discovered. We identified gene products that are important for the antiviral activity of interferon against vesicular stomatitis...
Cellular Response to Infection | SpotlightSTAT5: a Target of Antagonism by Neurotropic FlavivirusesFlaviviruses are a diverse group of insect-borne viruses responsible for numerous significant public health threats. Previously, we used a computational biology approach to define molecular signatures of antiviral DC responses following activation of innate immune signaling or infection with West Nile virus (WNV). In this work, we identify STAT5 as a regulator of DC activation and antiviral immune responses downstream of innate immune...
Pathogenesis and ImmunityComprehensive Mutagenesis of Herpes Simplex Virus 1 Genome Identifies UL42 as an Inhibitor of Type I Interferon InductionThis work is the first to report the use of a high-throughput mutagenesis method to study the genome of HSV-1. We report three novel viral proteins potentially involved in regulating the host type I interferon response. We describe a novel mechanism by which the viral protein UL42 is able to suppress the production of beta interferon. The tool we introduce in this study can be used to study the HSV-1 genome in great detail to better...
Cellular Response to Infection | SpotlightTRIM69 Inhibits Vesicular Stomatitis Indiana VirusVesicular stomatitis Indiana virus (VSIV) is a veterinary pathogen that is also used as a backbone for many oncolytic and vaccine strategies. In natural and therapeutic settings, viral infections like VSIV are sensed by the host, and as a result the host cells make proteins that can protect them from viruses. In the case of VSIV, these antiviral proteins constrain viral replication and protect most healthy tissues from virus infection....
Pathogenesis and ImmunityComparison of the Innate Immune Responses to Pathogenic and Nonpathogenic Clade B New World ArenavirusesNew World (NW) arenaviruses are a diverse family of emerging zoonotic viruses that merit significant attention as important public health problems. The close genetic relationship of nonpathogenic NW arenaviruses with their highly pathogenic cousins suggests that few mutations may be sufficient to enhance virulence. The identification of molecular determinants of virulence of NW arenaviruses is therefore of great importance. Here we...
Cellular Response to InfectionSuppression of Stromal Interferon Signaling by Human Papillomavirus 16The persistence of high-risk human papillomavirus (HPV) infections is the key risk factor for developing HPV-associated cancers. The ability of HPV to evade host immunity is a critical component of its ability to persist. The environment surrounding a tumor is increasingly understood to be critical in cancer development, including immune evasion. Our studies show that HPV can suppress the expression of immune-related genes in...
Cellular Response to InfectionCharacterization of Novel Splice Variants of Zinc Finger Antiviral Protein (ZAP)ZAP is an IFN-induced host factor that can inhibit a wide range of viruses, and there is great interest in fully characterizing its antiviral mechanism. This is the first study that defines the antiviral capacities of individual ZAP isoforms in the absence of endogenous ZAP expression and, hence, cross talk with other isoforms. Our data demonstrate that ZAP is expressed as four different forms: ZAPS, ZAPM, ZAPL, and ZAPXL. The longer...