replication
Pathogenesis and ImmunityMarek’s Disease Virus Requires Both Copies of the Inverted Repeat Regions for Efficient In Vivo Replication and PathogenesisMarek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes losses in the poultry industry of up to $2 billion per year. The virus is also widely used as a model to study alphaherpesvirus pathogenesis and virus-induced tumor development in a natural host. MDV and most other herpesviruses harbor direct or inverted repeats regions in their genome. However, the role of these sequence duplications in...
Virus-Cell InteractionsPotential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIVViruses have colonized the host germ line on many occasions during evolution to eventually become endogenous. Here, we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro. Our results indicate that isolated primary TGCs express alternative HIV-1 receptors, allowing virion binding but not entry. However, HIV-1 entered and integrated...
Virus-Cell InteractionsSphingomyelin Is Essential for the Structure and Function of the Double-Membrane Vesicles in Hepatitis C Virus RNA Replication FactoriesPrevious reports assumed that sphingomyelin (SM) is essential for HCV replication, but the mechanism was unclear. In this study, we showed for the first time that SM and ceramide transfer protein (CERT), which is in the SM biosynthesis pathway, are essential for the biosynthesis of double-membrane vesicles (DMVs), the sites of viral replication. Low numbers of DMVs were observed in CERT-KO cells transfected with replicon RNA or with...
Genome Replication and Regulation of Viral Gene ExpressionUnpaired Guanosines in the 5′ Untranslated Region of HIV-1 RNA Act Synergistically To Mediate Genome PackagingHIV-1 must package its RNA genome during virus assembly to generate infectious viruses. To better understand how HIV-1 packages its RNA genome, we examined the roles of RNA elements identified as binding sites for NC, a Gag-derived RNA-binding protein. Our results demonstrate that binding sites within stem-loop 1 of the 5′ untranslated region play important roles in genome packaging. Although mutating one or two NC-binding sites caused...
Genome Replication and Regulation of Viral Gene ExpressionPyk2 Regulates Human Papillomavirus Replication by Tyrosine Phosphorylation of the E2 ProteinHuman papillomaviruses are the major causative agents of cervical, oral, and anal cancers. The present study demonstrates that the Pyk2 tyrosine kinase phosphorylates E2 at tyrosine 131, interfering with genome replication. We provide evidence that phosphorylation of E2 prevents binding to the Brd4-CTM. Our findings add to the understanding of molecular pathways utilized by the virus during its vegetative life cycle and offers insights...
Genome Replication and Regulation of Viral Gene ExpressionReconstitution of an RNA Virus Replicase in Artificial Giant Unilamellar Vesicles Supports Full Replication and Provides Protection for the Double-Stranded RNA Replication IntermediateUnderstanding the mechanism of replication of positive-strand RNA viruses, which are major pathogens of plants, animals, and humans, can lead to new targets for antiviral interventions. These viruses subvert intracellular membranes for virus replication and coopt numerous host proteins, whose functions during virus replication are not yet completely defined. To dissect the roles of various host factors in Tomato bushy stunt virus...
Genome Replication and Regulation of Viral Gene ExpressionMutagenic Analysis of Hazara Nairovirus Nontranslated Regions during Single- and Multistep Growth Identifies both Attenuating and Functionally Critical Sequences for Virus ReplicationNairoviruses are a group of RNA viruses that include many serious pathogens of humans and animals, including one of the most serious human pathogens in existence, Crimean-Congo hemorrhagic fever virus. The ability of nairoviruses to multiply and cause disease is controlled in major part by nucleotides that flank the 3′ and 5′ ends of nairoviral genes, called nontranslated regions (NTRs). NTR nucleotides interact with other virus...
Virus-Cell Interactions | SpotlightA Genetically Engineered Rotavirus NSP2 Phosphorylation Mutant Impaired in Viroplasm Formation and Replication Shows an Early Interaction between vNSP2 and Cellular Lipid DropletsReverse genetics was used to generate a recombinant rotavirus with a single phosphomimetic mutation in nonstructural protein 2 (NSP2 S313D) that exhibits delayed viroplasm formation, delayed replication, and an interfering phenotype during coinfection with wild-type rotavirus, indicating the importance of this amino acid during virus replication. Exploiting the delay in viroplasm assembly, we found that viroplasm-associated NSP2...
Virus-Cell InteractionsRegulation of Mumps Virus Replication and Transcription by Kinase RPS6KB1Mumps virus is an important human pathogen. In recent years, MuV has reemerged in the United State, with outbreaks occurring in young adults who have been vaccinated. Our work provides insight into a previously unknown mumps virus-host interaction. RPS6KB1 negatively regulates MuV replication, likely through its interaction with the P protein. Understanding virus-host interactions can lead to novel antiviral drugs and enhanced vaccine...
Virus-Cell Interactions | SpotlightSwine ANP32A Supports Avian Influenza Virus PolymeraseAvian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but they only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus “mixing vessels.” In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different...