Annual Review of Virology最新文献

Inbred mouse strains are an invaluable resource for modeling virus-host interactions and studying how specific host genes affect virus-induced disease. However, many viruses cause a spectrum of disease outcomes in humans ranging from asymptomatic infection to severe disease or death. Conventional mouse strains do not recapitulate human genetic diversity and often fail to reproduce the full spectrum of virus-induced disease phenotypes seen in humans. The Collaborative Cross (CC) recombinant inbred mouse population is a genetically diverse set of mouse strains designed to model the genetic and phenotypic diversity seen in human populations. The CC has been used to study the effect of host genetic variation on the pathogenesis of several human viruses, and we review the utility of the CC as a resource both for developing new models of virus-induced disease and for the identification and study of host gene variants that affect susceptibility to virus-induced disease.

Bacteria have evolved a wide range of defense systems to combat phage infections. In the cheese industry, lactic acid bacteria (LAB) used for milk fermentation continuously face threats from phages. Therefore, selecting or developing industrial strains with enhanced phage resistance requires a focus on robust defense systems. Among these systems, the clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) are notably prevalent in LAB. The early characterization of this adaptive immune system was closely tied to the cheese industry, particularly with Streptococcus thermophilus in which CRISPR-Cas systems are ubiquitous and highly active. This review underscores the contributions of S. thermophilus and its virulent phages to our understanding of the function and mechanisms of CRISPR-Cas systems. Additionally, we review the diversity of CRISPR-Cas systems in LAB used in the cheese industry, the counter-defense strategies employed by dairy phages, and the applications of CRISPR-Cas systems within this sector.

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.

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.

My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements and professional challenges with the hope that they illustrate the joy of research and the need for resilience and persistence to assure progress and acceptance of unexpected results.

Grapevine red blotch disease emerged as a major threat to the North American viticulture more than 25 years ago. Prior to the discovery of its causal agent, grapevine red blotch virus (GRBV), the disease was likely mistaken for other vineyard problems. Over the last decade and a half, research on red blotch disease focused on GRBV biology; diagnostics; transmission biology; disease epidemiology; ecology of its vector, the treehopper Spissistilus festinus; and strategies for disease management. Research has also uncovered some of the physiological effects of GRBV on grapevines (inhibition of hexose translocation from leaves to fruits, transcriptional suppression of phenylpropanoid pathways), fruit (low soluble solids, poor ripening, reduced phenolic extractability, high titratable acidity), and wine (altered sensory attributes such as less fruit aromas and poor color and mouthfeel). The economic effects of the disease in different grape-producing regions of the United States are estimated to be as high as $68,548 per hectare over a 25-year vineyard lifespan. Here we reflect on major red blotch research progress and discuss future priorities. We also highlight the contribution of GRBV to the grapevine community as a major driver of enhanced cooperation among researchers, growers, nurseries, extension agents, policymakers, regulators, and service providers. We anticipate that strengthened interactions among all the members of the grapevine community and science-based disease management responses in vineyards will curtail GRBV spread and improve vineyard health.

The discovery of precursor messenger RNA splicing was made through the study of adenovirus in the 1970s, and since then, the role of splicing in viral infection has been an important area of study. However, most of the work in this area prior to the past decade has focused on the splicing of viral genes. Only recently has there been an explosion of studies investigating how viral infection influences the splicing of host genes and the effect of this regulation on host-viral interplay. This review focuses on this growing interest and understanding of how viruses affect host splicing, the functional consequences of this regulation, and the questions that are motivating ongoing research surrounding host splicing changes during viral infection.

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.

Alphaviruses are mosquito-borne, enveloped viruses with a positive-sense, single-stranded RNA genome. Alphaviruses enter host cells via receptor-mediated endocytosis, using various cellular surface receptors such as matrix remodeling-associated protein 8 (MXRA8), low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3), and very low-density lipoprotein receptor (VLDLR), which facilitate binding to the viral glycoproteins. Following entry, viral proteins are expressed and nonstructural proteins assemble into replication complexes in host cells, driving RNA synthesis and genome replication. Viral assembly occurs at the plasma membrane, where nascent virions bud from the host cell in a process driven by capsid and spike proteins. Recent combinatorial structural studies have provided detailed molecular insights into various steps of the alphavirus life cycle. These structural insights into the alphavirus life cycle enhance our understanding of viral replication and assembly, with significant implications for antiviral strategies and the development of alphavirus-based vaccine vectors.