Annual Review of Virology最新文献

The morbidity and mortality associated with viral diseases in plants, animals, and humans are significant concerns. Understanding how viruses cause disease and identifying the viral and host factors that determine the outcome of infection are essential to develop new antiviral therapeutics and strategies to induce protective immunity. In this review, we focus on the transformative potential of spatial transcriptomics for studies of viral pathogenesis and some of the intricacies of corresponding technologies and how to implement them.

Flaviviruses represent major human pathogens transmitted by arthropod vectors, causing significant morbidity and mortality worldwide. Morphogenesis-the assembly and maturation of infectious flavivirus particles-is a complex process that occurs in association with host cell membranes and requires extensive cellular remodeling. This review examines recent advances in our understanding of flavivirus morphogenesis, from the molecular mechanisms driving virion assembly to their implications for viral pathogenesis. We discuss how viral proteins orchestrate the assembly process through interactions with the host cell machinery, particularly focusing on membrane reorganization, lipid metabolism, and post-translational modifications. The production of structurally heterogeneous viral particles is a key feature of flavivirus morphogenesis with important consequences for immune recognition and viral fitness. Understanding these fundamental aspects of the flavivirus life cycle has led to new insights into virus-host interactions and highlights promising targets for therapeutic intervention.

The rapidly evolving pace of scientific information, technology, and innovation in pedagogical approaches provides an opportunity to consider the future of virology education. Virology curriculum guidelines for undergraduate and graduate education call for student-centered approaches with a focus on integrating concepts by virology topics rather than by virus family. Through backward design, courses should be structured based on desired student learning outcomes in virology, and then the process and content should be developed to align with the learning goals. Learning goals and content in graduate virology education place additional emphasis on skill building and higher-order analysis. Evidence-based teaching practices favor active-learning strategies that promote student engagement and critical thinking such as group work, journal club discussions, and experiential learning over a lecture-based education model. Teaching approaches should also foster the establishment of supportive learning environments that meet the needs of a varied population of learners and promote belonging in the virology community.

Subcellular organelles are dynamic structures that tune their functions in conjunction with changes to their shapes and compositions. Each organelle has distinct structure-function relationships that change in response to diverse stimuli. Such remodeling events further affect organelle-organelle interaction networks facilitated by membrane contact sites, thereby activating rapid intra- and intercellular communication cascades. As viruses rely on repurposing the host cell machinery during infections, organelle remodeling is a fundamental facet and outcome of all viral infections. Some organelle remodeling events are unique to particular viruses, while others are shared by an array of viruses. Here, we review knowledge derived from this expanding yet still underexplored research area of infection-induced organelle remodeling. We focus on the molecular mechanisms used by viruses to temporally control organelle structure-function relationships. We highlight how organelle remodeling can inhibit host defenses or facilitate specific stages of a virus replication cycle, i.e., entry, replication, assembly, and spread.

Viruses and the hosts they parasitize are engaged in a perpetual tug-of-war that is fought at multiple virus-host interfaces from the cell surface to the nucleus. It is increasingly clear that structured RNA elements represent major players and conduits at the forefront of this push and pull. Viral RNA structures hijack or subvert host RNA polymerases; ribosomes; translation-associated enzymes; RNA processing, modification, and transport systems; antiviral immunity proteins; and more. Recent advances in visualizing complex RNA and ribonucleoprotein structures at the virus-host interfaces have provided timely new insights into molecular mechanisms of viral exploitation, host defense, and viral counter-defense. Through the lens of RNA structure and recognition, we compare and analyze a representative set of such interfaces to discern general patterns and recurring strategies. We find that virus-host interfaces frequently have their roots or doppelgängers in the existing cellular interfaces. This suggests widespread viral mimicry of cellular interfaces and interactions. Viral RNAs further borrow and amalgamate distinct features from several host RNAs to form chimeras, which simultaneously target multiple host systems for viral gains.

Influenza virus is a segmented, single-stranded, negative-sense RNA virus. Viral genome transcription (to make viral messenger RNA) and replication (to make more viral genome) of influenza virus are catalyzed by the influenza viral RNA-dependent RNA polymerase (FluPol) in the context of the viral ribonucleoprotein complexes in the nucleus of infected cells. The dynamics of the transcription and replication are tightly regulated throughout the viral life cycle, with a switch from transcription to replication in the later stages of infection being essential for efficient progeny virus production. The mechanism by which the virus achieves the switch has emerged recently through structural and functional studies. Here, we summarize the current hypotheses of the regulatory mechanisms governing the switch. Specifically, we highlight our recent findings showing that the late expression of the viral nonstructural protein NS2, which resulted from a suboptimal splicing site in the NS segment, functions as a molecular timer to mediate the transcription-to-replication switch.

Influenza A viruses (IAVs) typically cause a mild to moderate respiratory disease, whereas infections with pandemic and highly pathogenic avian IAV strains are frequently associated with high morbidity and death. Various noncanonical or aberrant transcription and replication products have been implicated in the effect of IAV infection on disease outcomes. While early research indicated that all these molecules may be defective, recent findings coupled with analyses of the structure of the IAV RNA polymerase suggest that the production of noncanonical RNAs is not solely driven by errors. Instead, their place in infection may be more nuanced. In this review, we discuss our current understanding of the molecular steps that underlie noncanonical transcription and replication and which molecular mysteries remain.

The negative effects of potyvirus diseases on the agricultural industry are extensive and global. Understanding how protein-protein interactions contribute to potyviral infections is imperative to developing resistant varieties that help counter the threat potyviruses pose. While many protein-protein interactions have been reported, only a fraction are essential for potyviral infection. Accumulating evidence demonstrates that potyviral infection processes are interconnected. For instance, the interaction between the eukaryotic initiation factor 4E (eIF4E) and viral protein genome-linked (VPg) is crucial for both viral translation and protecting viral RNA (vRNA). Additionally, recent evidence for open reading frames on the reverse-sense vRNA and for nonequimolar expression of viral proteins has challenged the previous polyprotein expression model. These discoveries will surely reveal more about the potyviral protein interactome. In this review, we present a synthesis of the potyviral infection cycle and discuss influential past discoveries and recent work on protein-protein interactions in various infection processes.

Once inside host cells, retroviruses generate a double-stranded DNA copy of their RNA genomes via reverse transcription inside a viral core, and this viral DNA is subsequently integrated into the genome of the host cell. Before integration can occur, the core must cross the cell cortex, be transported through the cytoplasm, and enter the nucleus. Retroviruses have evolved different mechanisms to accomplish this journey. This review examines the various mechanisms retroviruses, especially HIV-1, have evolved to commute throughout the cell. Retroviruses cross the cell cortex while modulating actin dynamics and use microtubules as roads while connecting with microtubule-associated proteins and motors to reach the nucleus. Although a clearer picture exists for HIV-1 compared with other retroviruses, there is still much to learn about how retroviruses accomplish their commute.