Annual Review of Virology - Current Issue

Plant viruses present significant challenges to global agriculture, causing crop losses, threatening food security, and imposing economic burdens. Advances in biotechnology have revolutionized strategies to attack these threats, with genetically modified and genome-edited virus-resistant plants, developed using precision tools such as RNA interference and CRISPR/Cas technology, playing pivotal roles. Despite these breakthroughs, fragmented regulatory frameworks and divergent policies across regions including the European Union and the Global South hinder the global adoption of such innovations. Multifaceted approaches, including gene pyramiding, microbiome-based strategies, and pathogen-targeted defenses, show promise for enhancing plant resilience. This review explores the biological, regulatory, and ethical dimensions of deploying virus-resistant crops, emphasizing the need for harmonization of international regulation to maximize biotechnological benefits. By addressing these challenges, biotechnology can advance sustainable agriculture, secure food systems, and mitigate the effect of plant viral diseases.

Emerging and re-emerging mosquito-borne viruses pose a significant threat to global public health. Unfortunately, effective preventive and therapeutic measures are scarce. An in-depth understanding of the mechanisms regulating viral pathogenesis, vector competence, and viral transmission between mammalian hosts and vectors may lay the foundations for new preventive and therapeutic approaches. Here, we summarize the intricate interactions between commensal microbes and mosquito-borne viruses in mammalian hosts and mosquitoes, including how the host gut microbiota influences the pathogenesis of viral infection; how the host skin microbiota affects the attractiveness of hosts to mosquitoes and viral transmission; and how symbiotic microbes, including endosymbiotic bacteria, fungi, and insect-specific viruses in mosquitoes, regulate viral transmission through gut immune regulation and microbe-derived effectors. In addition, we discuss the potential of symbiotic microbe-based interventions to suppress the transmission of mosquito-borne viral diseases.

The recent global spread of mpox virus, facilitated by a newly established human-to-human transmission mode, has rekindled interest in poxviruses and the molecular factors defining their host range. Poxviruses employ host-range factors, a subset of their immune evasion proteins, to overcome cell-intrinsic defenses in specific cell types or host species. Over the past decade, investigations of these factors have revealed previously unrecognized antiviral mechanisms and expanded our understanding of innate immunity. Among the key developments are the discovery of novel restriction factors, including SAMD9 and SAMD9L (SAMD9/9L), and expanded roles for established antiviral proteins such as IFITs, FAM111A, and ZAP. These advances not only clarify how poxvirus host range is determined but also offer valuable insights into the complexity and evolution of mammalian innate immunity. Here, I highlight new findings on poxvirus host-range determinants, with a particular focus on SAMD9/9L and the three distinct classes of poxvirus host-range factors that antagonize them.

Environmental surveillance, including wastewater and air sampling, has emerged as a powerful complement to traditional clinical surveillance for monitoring viral circulation. Advances in sampling and detection technologies, many spurred by the COVID-19 pandemic, have enabled more sensitive and comprehensive characterization of viruses in diverse types of commingled samples from multiple individuals. Expanding environmental monitoring globally presents challenges and opportunities, particularly in low- and middle-income countries where centralized sewage infrastructure may be limited. Ethical implementation will require balancing privacy and transparency through community engagement. Future directions include using environmental surveillance to detect emerging zoonoses, fill gaps when clinical testing wanes, and inform public health actions. While logistical, regulatory, and ethical challenges remain, coordination across scientific and public health stakeholders can enable environmental monitoring to transform epidemic intelligence. This review summarizes recent developments in environmental surveillance systems and discusses how they can mitigate the introduction and spread of viruses in communities.

The evolution of pathogen virulence is a central question in evolutionary epidemiology. This review examines the development of these ideas over the last 75 years from an ecological perspective using a mixture of theoretical and empirical studies. I begin with Fenner's work on myxomatosis, which led to the key concept that trade-offs exist between transmission and virulence in pathogen life histories. I then consider how models of Fenner's study gradually developed into a major area of theoretical epidemiology. The emerging concepts were constantly challenged by new empirical studies that illustrated how virulence may be modified by culling, vaccination, and different forms of heterogeneity within and between species and spatial heterogeneity. The emerging field of phylodynamics has provided multiple new tools to analyze and visualize the evolution of virulence and a much broader perspective on the diversity of viruses and their hosts. I conclude with a brief discussion of possible future directions of study.

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.

The expansion of viruses within cells requires efficient viral protein production. Counterintuitively, many viral genomes are enriched in suboptimal codons, which are typically associated with reduced protein outputs. Recent research using chikungunya virus (CHIKV) as a prototype model highlights the role of host transfer RNA (tRNA) modifications, collectively known as the tRNA epitranscriptome, in resolving this paradox. Upon infection, CHIKV triggers a DNA damage stress response that ultimately leads to changes in the tRNA epitranscriptome. These changes reprogram codon optimality, selectively enhancing the translation of specific suboptimal codons that are highly enriched in both host stress response genes and the viral genome. Hence, CHIKV codon usage optimally aligns with the tRNA modification landscape in infected cells. We propose that this interplay between viral codon usage, stress responses, and tRNA modifications is a shared strategy among viruses beyond CHIKV. Targeting this interplay may pave the way for the development of broad-spectrum antiviral therapies.

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.

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.

A common cause of acute hepatitis in humans, hepatitis A virus (HAV) replicates within hepatocytes without inducing cytopathology. Virus is released from infected cells in the absence of cell lysis as quasi-enveloped HAV (eHAV) virions cloaked in host membranes. These virions circulate in blood when exported across the basolateral membrane of hepatocytes but are stripped of their membranes by bile salts when exported across the apical membrane into the biliary system resulting in fecal shedding of abundant naked, nonenveloped virus. This review summarizes the composition and structure of these two distinct types of infectious extracellular hepatovirus virions and outlines the evidence for specific signals within HAV capsid proteins that mediate interactions with the endosomal sorting complexes required for transport (ESCRT). Capsid protein interactions with the ESCRT-associated proteins ALIX and HD-PTP play a crucial role in the budding of newly assembled capsids into multivesicular endosomes, the first step in nonlytic release of quasi-enveloped virions from infected cells. This review also considers how eHAV virions enter naïve cells to establish infection in the absence of a virally encoded protein on their surface and compares the role played by quasi-envelopment in the hepatovirus life cycle with the nonlytic release of other types of viruses in extracellular vesicles.