Current opinion in virology最新文献

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematologic malignancy linked to HTLV-1 infection, which is refractory to therapy. The precise mechanism of oncogenesis in ATLL is incompletely understood, however, oncogenic viral genes Tax and Hbz are implicated, and recent large genomic and transcriptome studies provide further insight. Despite progress in understanding the disease, survival and outcome with current therapies remain poor. Long-term survivors are reported, primarily among those with indolent disease or activating CC chemokine receptor 4 mutations, however, allogeneic hematopoietic stem cell transplant is the only curative treatment option. The majority of patients succumb to their disease and ongoing and collaborative research efforts are needed. I will review recent updates in HTLV-1-associated ATLL epidemiology, pathogenesis, therapy, and prevention.

Global metagenomic surveys have revealed that bats host a diverse array of paramyxoviruses, including species from at least five major genera. An essential determinant of successful spillover is the entry of a virus into a new host. We evaluate the role of receptor usage in the zoonotic potential of bat-borne henipaviruses, morbilliviruses, pararubulaviruses, orthorubulaviruses, and jeilongviruses; successful spillover into humans depends upon compatibility of a respective viral attachment protein with its cognate receptor. We also emphasize the importance of postentry restrictions in preventing spillover. Metagenomics and characterization of newly identified paramyxoviruses have greatly improved our understanding of spillover determinants, allowing for better forecasts of which bat-borne viruses may pose the greatest risk for cross-species transmission into humans.

The capacity of host cells to detect and restrict an infecting virus rests on an array of cell-autonomous antiviral effectors and innate immune receptors that can trigger inflammatory processes at tissue and organismal levels. Dynamic changes in protein abundance, subcellular localisation, post-translational modifications and interactions with other biomolecules govern these processes. Proteomics is therefore an ideal experimental tool to discover novel mechanisms of host antiviral immunity. Additional information can be gleaned both about host and virus by systematic analysis of viral immune evasion strategies. In this review, we summarise recent advances in proteomic technologies and their application to antiviral innate immunity.

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.