Current opinion in virology最新文献

The Bunyavirales order is the largest grouping of RNA viruses, comprising emerging and re-emerging human, plant and animal pathogens. Bunyaviruses have a global distribution and many members of the order are transmitted by arthropods. They have evolved a plethora of mechanisms to manipulate the regulatory processes of the infected cell to facilitate their own replicative cycle, in hosts of disparate phylogenies. Interest in virus-vector interactions is growing rapidly. However, current understanding of tick-borne bunyavirus cellular interaction is heavily biased to studies conducted in mammalian systems. In this short review, we summarise current understandings of how tick-borne bunyaviruses utilise major cellular pathways (innate immunity, apoptosis and RNAi responses) in mammalian or tick cells to facilitate virus replication.

The COVID-19 pandemic has accelerated the development of nucleoside analogs to treat respiratory virus infections, with remdesivir being the first compound to receive worldwide authorization and three other nucleoside analogs (i.e. favipiravir, molnupiravir, and bemnifosbuvir) in the pipeline. Here, we summarize the current knowledge concerning their clinical efficacy in suppressing the virus and reducing the need for hospitalization or respiratory support. We also mention trials of favipiravir and lumicitabine, for influenza and respiratory syncytial virus, respectively. Besides, we outline how nucleoside analogs interact with the polymerases of respiratory viruses, to cause lethal virus mutagenesis or disturbance of viral RNA synthesis. In this way, we aim to convey the key findings on this rapidly evolving class of respiratory virus medication.

Poxviruses are a diverse family of double-stranded DNA viruses that cause mild-to-severe disease in selective hosts, including humans. Although most poxviruses are restricted to their hosts, some members can leap host species and cause zoonotic diseases and, therefore, are genuine threats to human and animal health. The recent global spread of monkeypox in humans suggests that zoonotic poxviruses can adapt to a new host, spread rapidly in the new host, and evolve to better evade host innate barriers. Unlike many other viruses, poxviruses express an extensive repertoire of self-defense proteins that play a vital role in the evasion of host innate and adaptive immune responses in their newest host species. The function of these viral immune modulators and host-specific cytokine responses can result in different host tropism and poxvirus disease progression. Here, we review the role of different cytokines that control poxvirus host tropism and adaptation.

Under constant barrage by viruses, hosts have evolved a plethora of antiviral effectors and defense mechanisms. To survive, viruses must adapt to evade or subvert these defenses while still capturing cellular resources to fuel their replication cycles. Large-scale studies of the antiviral activities of cellular proteins and processes have shown that different viruses are controlled by distinct subsets of antiviral genes. The remaining antiviral genes are either ineffective in controlling infection, or in some cases, actually promote infection. In these cases, classically defined antiviral factors are retasked by viruses to enhance viral replication. This creates a more nuanced picture revealing the contextual nature of antiviral activity. The same protein can exert different effects on replication, depending on multiple factors, including the host, the target cells, and the specific virus infecting it. Here, we review numerous examples of viruses hijacking canonically antiviral proteins and retasking them for proviral purposes.

Poxviruses are large double-stranded DNA viruses that encode their own DNA replication, transcription, and mRNA biogenesis machinery, which underlies their ability to replicate entirely in the cytoplasm. However, like all other viruses, poxviruses remain dependent on host ribosomes to translate their mRNAs into the viral proteins needed to complete their replication cycle. While earlier studies established a fundamental understanding of how poxviruses wrestle with their hosts for control of translation initiation and elongation factors that guide ribosome recruitment and mRNA decoding, recent work has begun to reveal the extent to which poxviruses directly target the ribosome itself. This review summarizes our current understanding of the regulation of ribosomes and translation in poxvirus infection.

Control of gene expression, including transcription, is central in dictating the outcome of viral infection. One of the profound alterations induced by viruses is modification to the integrity and function of eukaryotic RNA polymerase II (Pol II). Here, we discuss how infection perturbs the Pol II complex by altering subunit phosphorylation and turnover, as well as how cellular genotoxic stress (e.g. DNA damage) elicits similar outcomes. By highlighting emerging parallels and differences in Pol II control during viral infection and abiotic stress, we hope to bolster identification of pathways that target Pol II and regulate the transcriptome.

The intimate relationship between virus and host cell can result in highly adapted viruses that are restricted to a single host. However, some viruses have the ability to infect multiple host species. Remarkably, hepatitis E viruses (HEV) comprise genotypes that are either ‘single-host’ or ‘multi-host’ genotypes, a trait that raises fundamental questions: Why do different genotypes differ in their host range, despite a high degree of genomic similarity? What are the underlying molecular determinants that shape species barriers? Here, we review the current knowledge of viral and host determinants that may affect the evolutionary trajectories of HEV. We also provide a perspective on techniques and methods that address open questions of HEV host range and adaptation.

Herpesviruses, such as Epstein–Barr virus (EBV), encode multiple viral microRNAs that are expressed throughout various infection stages. While much progress has been made in evaluating both the viral and host microRNAs (miRNAs) that are detected during infection as well as elucidating their molecular targets in vitro, our understanding of their contributions to pathogenesis in vivo, viral oncogenesis, and clinical implications for these small molecules remains limited. miRNAs are widely recognized as key regulators of global cellular processes, including apoptosis, cell differentiation, and development of immune responses. This review discusses the roles of miRNAs in EBV infection and current advances in miRNA-based diagnostic and therapeutic strategies potentially applicable toward EBV-associated diseases.

Positive-strand RNA viruses replicate in intracellular membranous structures formed after virus-driven intensive manipulation of subcellular organelles and membranes. These unique structures are called viral-replication organelles (VROs). To build VROs, the replication proteins coded by (+)RNA viruses co-opt host proteins, including membrane-shaping, lipid synthesis, and lipid-modification enzymes to create an optimal microenvironment that (i) concentrates the viral replicase and associated host proteins and the viral RNAs; (ii) regulates enzymatic activities and spatiotemporally the replication process; and (iii) protects the viral RNAs from recognition and degradation by the host innate immune defense. Tomato bushy stunt virus (TBSV), a plant (+)RNA virus, serves as an advanced model to study the interplay among viral components, co-opted host proteins, lipids, and membranes. This review presents our current understanding of the complex interaction between TBSV and host with panviral implications.