The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.
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http://dx.doi.org/10.3390/v8040102 | DOI Listing |
Virulence
December 2025
Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou, China.
Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed "host shutoff." Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes.
View Article and Find Full Text PDFDouble-stranded RNAs (dsRNAs) produced during viral infections are recognized by the innate immune sensor protein kinase R (PKR), triggering a host translation shutoff that inhibits viral replication and propagation. Given the harmful effects of uncontrolled PKR activation, cells must tightly regulate PKR to ensure that its activation occurs only in response to viral infections, not endogenous dsRNAs. Here, we use CRISPR-Translate, a FACS-based genome-wide CRISPR-Cas9 knockout screening method that exploits translation levels as a readout and identifies PACT as a key inhibitor of PKR during viral infection.
View Article and Find Full Text PDFJ Virol
November 2024
Guangdong Technological Engineering Research Center for Pets, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, China.
Unlabelled: Canine parvovirus type 2 (CPV-2) is a member of the Parvoviridae family, characterized by its small, non-enveloped virions containing a linear single-stranded DNA genome of approximately 5 kb. Parvoviruses entirely reliant on the host cell's division machinery for replication. In this study, we demonstrate that CPV-2 infection triggers the host translation shutoff, a process in which the nonstructural protein 1 (NS1) plays a pivotal role.
View Article and Find Full Text PDFCommun Biol
November 2024
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Sciences, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China.
The recently identified novel duck reovirus (NDRV) is a waterfowl reovirus that can seriously harm or kill various waterfowl species. However, how NDRV interacts with host cells in Muscovy ducklings beyond the typical pathogenesis resulting from a viral infection is unknown. The current study examined the global translation efficiency of the Fabricius bursa of Muscovy ducklings infected with NDRV HN10 using mass spectrometry and ribosome footprint sequencing.
View Article and Find Full Text PDFMem Inst Oswaldo Cruz
October 2024
Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Imunofarmacologia, Rio de Janeiro, RJ, Brasil.
Background: Herpesviruses are common co-pathogens in individuals infected with human immunodeficiency virus (HIV). Herpes simplex virus type 1 (HSV1) enhances HIV-1 replication and has evolved mechanisms to evade or disrupt host innate immune responses, including interference with interferon (IFN) signalling pathways.
Objectives: The aimed of this work was evaluated whether it HSV1 affects HIV-1 replication through the modulation of the IFN pathway in human macrophages.
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