innate immunity
Virus-Cell InteractionsInnate Intracellular Antiviral Responses Restrict the Amplification of Defective Virus Genomes of Parainfluenza Virus 5Copyback defective virus genomes (DVGs) are powerful inducers of innate immune responses both in vitro and in vivo. They impact the outcome of natural infections, may help drive virus‐host coevolution, and promote virus persistence. Due to their potent interfering and immunostimulatory properties, DVGs may also be used therapeutically as antivirals and vaccine adjuvants. However, little is known of the host cell...
Pathogenesis and ImmunityInsights into the Role of Innate Immunity in Cervicovaginal Papillomavirus Infection from Studies Using Gene-Deficient MicePapillomaviruses infect stratified squamous epithelia, and the viral life cycle is linked to epithelial differentiation. Additionally, changes occur in viral and host gene expression, and immune cells are activated to modulate the infectious process. In vitro studies with keratinocytes cannot fully model the complex viral and host responses and do not reflect the contribution of local and migrating immune cells. We show that...
Virus-Cell Interactions | SpotlightLoss of IKK Subunits Limits NF-κB Signaling in Reovirus-Infected CellsHost cells mount a response to curb virus replication in infected cells and prevent spread of virus to neighboring, as yet uninfected, cells. The NF-κB family of proteins is important for the cell to mediate this response. In this study, we show that in cells infected with mammalian reovirus, NF-κB is inactive. Further, we demonstrate that NF-κB is rendered inactive because virus infection results in reduced levels of upstream...
Pathogenesis and ImmunityThe Microbiota Contributes to the Control of Highly Pathogenic H5N9 Influenza Virus Replication in DucksDucks are frequently infected with avian influenza viruses belonging to multiple subtypes. They represent an important reservoir species of avian influenza viruses, which can occasionally be transmitted to other bird species or mammals, including humans. Ducks thus have a central role in the epidemiology of influenza virus infection. Importantly, ducks usually show little or no clinical signs even following infection with a highly...
Pathogenesis and ImmunityMechanisms of Endogenous HIV-1 Reactivation by Endocervical Epithelial CellsA reason that there is no universal cure for HIV-1 is that the virus can hide in the genome of infected cells in the form of latent proviral DNA. This hidden provirus is protected from antiviral drugs until it eventually reactivates to produce new virions. It is not well understood where in the body or how this reactivation occurs. We studied HIV-1 reactivation in the female genital tract, which is often the portal of HIV-1 entry and...
Virus-Cell InteractionsReverse Genetics Reveals a Role of Rotavirus VP3 Phosphodiesterase Activity in Inhibiting RNase L Signaling and Contributing to Intestinal Viral Replication In VivoRotaviruses are significant human pathogens that result in diarrhea, dehydration, and deaths in many children around the world. Rotavirus vaccines have suboptimal efficacy in low- to middle-income countries, where the burden of the diseases is the most severe. With the ultimate goal of improving current vaccines, we aim to better understand how rotavirus interacts with the host innate immune system in the small intestine. Here, we...
Pathogenesis and ImmunitySystemic Expression of a Viral RdRP Protects against Retrovirus Infection and DiseaseImmune control of retroviruses is notoriously difficult, a fundamental problem that has been most clinically consequential with the HIV-1 pandemic. As humans expand further into previously uninhabited areas, the likelihood of new zoonotic retroviral exposures increases. The role of the innate immune system, including ISGs, in controlling retroviral infections is currently an area of intensive study. This work provides evidence that a...
Cellular Response to InfectionMitochondrial and Innate Immunity Transcriptomes from Spodoptera frugiperda Larvae Infected with the Spodoptera frugiperda AscovirusAscoviruses are large DNA viruses that infect insects, inducing a cellular pathology that resembles apoptosis but which differs by causing enormous cellular hypertrophy followed by cleavage of the cell into numerous viral vesicles for replication. Previous EM studies suggest that mitochondria are important for vesicle formation. Transcriptome analyses of Spodoptera...
Virus-Cell InteractionsADAR2 Is Involved in Self and Nonself Recognition of Borna Disease Virus Genomic RNA in the NucleusCells use the editing activity of adenosine deaminase acting on RNA proteins (ADARs) to prevent autoimmune responses induced by self dsRNA, but viruses can exploit this process to their advantage. Borna disease virus (BoDV), a nuclear-replicating RNA virus, must escape nonself RNA sensing by the host to establish persistent infection in the nucleus. We evaluated whether BoDV utilizes ADARs to prevent innate immune induction. ADAR2 plays...
Virus-Cell InteractionsCpG Dinucleotides Inhibit HIV-1 Replication through Zinc Finger Antiviral Protein (ZAP)-Dependent and -Independent MechanismsSome RNA virus genomes are suppressed in the nucleotide combination of a cytosine followed by a guanosine (CpG), indicating that they are detrimental to the virus. The antiviral protein ZAP binds viral RNA containing CpGs and prevents the virus from multiplying. However, it remains unknown how the number and position of CpGs in viral genomes affect restriction by ZAP and whether CpGs have other antiviral mechanisms. Importantly,...