Annual Review of Virology最新文献

The bacteriolytic character of bacteriophages was employed as antibacterial therapy almost from the time of their discovery in 1917. In the United States, phage therapy was sporadic during the 1920s and 1930s but had dwindled into obscurity by the post-WWII period. This demise of phage therapy has traditionally been attributed to the superiority of antibiotics, discovered and first used during the war years, but this explanation is complicated by the fact that phage therapy outside the United States has had a longer and more successful life, especially in the countries of Eastern Europe. This review considers another, probably synergetic factor that was specific to the medical uses of phage in the United States: the geopolitical climate fostered by the Cold War reaction against Soviet science and its associated specter, socialized medicine. This analysis suggests that even such a purely scientific matter involving bacterial viruses cannot escape social forces and political ideologies.

The nucleoplasm, the cytosol, the inside of virions, and again the cytosol comprise the world in which the capsids of alphaherpesviruses encounter viral and host proteins that support or limit them in performing their tasks. Here, we review the fascinating conundrum of how specific protein-protein interactions late in alphaherpesvirus infection orchestrate capsid nuclear assembly, nuclear egress, and cytoplasmic envelopment, but target incoming capsids to the nuclear pores in naive cells to inject the viral genomes into the nucleoplasm for viral transcription and replication. Multiple capsid interactions with viral and host proteins have been characterized using viral mutants and assays that reconstitute key stages of the infection cycle. Keratinocytes, fibroblasts, mucosal epithelial cells, neurons, and immune cells employ cell type-specific intrinsic and cytokine-induced resistance mechanisms to restrict several stages of the viral infection cycle. However, concomitantly, alphaherpesviruses have evolved countermeasures to ensure efficient capsid function during infection.

Biomolecular condensates are nonmembrane-bound assemblies of biological polymers such as protein and nucleic acids. An increasingly accepted paradigm across the viral tree of life is (a) that viruses form biomolecular condensates and (b) that the formation is required for the virus. Condensates can promote viral replication by promoting packaging, genome compaction, membrane bending, and co-opting of host translation. This review is primarily concerned with exploring methodologies for assessing virally encoded biomolecular condensates. The goal of this review is to provide an experimental framework for virologists to consider when designing experiments to (a) identify viral condensates and their components, (b) reconstitute condensation cell free from minimal components, (c) ask questions about what conditions lead to condensation, (d) map these questions back to the viral life cycle, and (e) design and test inhibitors/modulators of condensation as potential therapeutics. This experimental framework attempts to integrate virology, cell biology, and biochemistry approaches.

Viruses exploit key host cell factors to accomplish each individual stage of the viral replication cycle. To understand viral pathogenesis and speed the development of new antiviral strategies, high-resolution visualization of virus-host interactions is needed to define where and when these events occur within cells. Here, we review state-of-the-art live cell imaging techniques for tracking individual stages of viral life cycles, focusing predominantly on retroviruses and especially human immunodeficiency virus type 1, which is most extensively studied. We describe how visible viruses can be engineered for live cell imaging and how nonmodified viruses can, in some instances, be tracked and studied indirectly using cell biosensor systems. We summarize the ways in which live cell imaging has been used to dissect the retroviral life cycle. Finally, we discuss select challenges for the future including the need for better labeling strategies, increased resolution, and multivariate systems that will allow for the study of full viral replication cycles.

South American ecosystems host astonishing biodiversity, with potentially great richness in viruses. However, these ecosystems have not yet been the source of any widespread, epidemic viruses. Here we explore a set of putative causes that may explain this apparent paradox. We discuss that human presence in South America is recent, beginning around 14,000 years ago; that few domestications of native species have occurred; and that successive immigration events associated with Old World virus introductions reduced the likelihood of spillovers and adaptation of local viruses into humans. Also, the diversity and ecological characteristics of vertebrate hosts might serve as protective factors. Moreover, although forest areas remained well preserved until recently, current brutal, sudden, and large-scale clear cuts through the forest have resulted in nearly no ecotones, which are essential for creating an adaptive gradient of microbes, hosts, and vectors. This may be temporarily preventing virus emergence. Nevertheless, the mid-term effect of such drastic changes in habitats and landscapes, coupled with explosive urbanization and climate changes, must not be overlooked by health authorities.

Interferon lambda (IFN-λ, type III IFN, IL-28/29) is a family of antiviral cytokines that are especially important at barrier sites, including the maternal-fetal interface. Recent discoveries have identified important roles for IFN-λ during pregnancy, particularly in the context of congenital infections. Here, we provide a comprehensive review of the activity of IFN-λ at the maternal-fetal interface, highlighting cell types that produce and respond to IFN-λ in the placenta, decidua, and endometrium. Further, we discuss the role of IFN-λ during infections with congenital pathogens including Zika virus, human cytomegalovirus, rubella virus, and Listeria monocytogenes. We discuss advances in experimental models that can be used to fill important knowledge gaps about IFN-λ-mediated immunity.

Before the very recent discovery of umbra-like viruses (ULVs), the signature defining feature of all plant RNA viruses was the encoding of specialized RNA-binding movement proteins (MPs) for transiting their RNA genomes through gated plasmodesmata to establish systemic infections. The vast majority of ULVs share umbravirus-like RNA-dependent RNA polymerases and 3'-terminal structures, but they differ by not encoding cell-to-cell and long-distance MPs and by not relying on a helper virus for trans-encapsidation and plant-to-plant transmission. The recent finding that two groups of ULVs do not necessarily encode MPs is expanding our understanding of the minimum requirements for modern plant RNA viruses. ULV CY1 from citrus uses host protein PHLOEM PROTEIN 2 (PP2) for systemic movement, and related ULVs encode a capsid protein, thereby providing an explanation for the lack of helper viruses present in many ULV-infected plants. ULVs thus resemble the first viruses that infected plants, which were likely deposited from feeding organisms and would have similarly required the use of host proteins such as PP2 to exit initially infected cells.

The arrival of novel sequencing technologies throughout the past two decades has led to a paradigm shift in our understanding of herpesvirus genomic diversity. Previously, herpesviruses were seen as a family of DNA viruses with low genomic diversity. However, a growing body of evidence now suggests that herpesviruses exist as dynamic populations that possess standing variation and evolve at much faster rates than previously assumed. In this review, we explore how strategies such as deep sequencing, long-read sequencing, and haplotype reconstruction are allowing scientists to dissect the genomic composition of herpesvirus populations. We also discuss the challenges that need to be addressed before a detailed picture of herpesvirus diversity can emerge.

Of the thousands of viruses infecting humans, only seven cause cancer in the general population. Tumor sequencing is now a common cancer medicine procedure, and so it seems likely that more human cancer viruses already would have been found if they exist. Here, we review cancer characteristics that can inform a dedicated search for new cancer viruses, focusing on Kaposi sarcoma herpesvirus and Merkel cell polyomavirus as the most recent examples of successful genomic and transcriptomic searches. We emphasize the importance of epidemiology in determining which cancers to examine and describe approaches to virus discovery. Barriers to virus discovery, such as novel genomes and viral suppression of messenger RNA expression, may exist that prevent virus discovery using existing approaches. Optimally virus hunting should be performed in such a way that if no virus is found, the tumor can be reasonably excluded from having an infectious etiology and new information about the biology of the tumor can be found.