Annual Review of Virology最新文献

As obligate intracellular parasites, all viruses must co-opt cellular machinery to facilitate their own replication. Viruses often co-opt these cellular pathways and processes through physical interactions between viral and host proteins. In addition to facilitating fundamental aspects of virus replication cycles, these virus-host protein interactions can also disrupt physiological functions of host proteins, causing disease that can be advantageous to the virus or simply a coincidence. Consequently, unraveling virus-host protein interactions can serve as a window into molecular mechanisms of virus replication and pathogenesis. Identifying virus-host protein interactions using unbiased systems biology approaches provides an avenue for hypothesis generation. This review highlights common systems biology approaches for identification of virus-host protein interactions and the mechanistic insights revealed by these methods. We also review conceptual innovations using comparative and integrative systems biology that can leverage global virus-host protein interaction data sets to more rapidly move from hypothesis generation to mechanism.

Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in infants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to a significant disease burden in immunocompromised individuals. Hence, an effective HCMV vaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, despite more than five decades of vaccine development, no successful HCMV vaccine is available. This review summarizes what we have learned from acquired natural immunity, including innate and adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the progress in related animal models; and the analysis of protective immune responses during natural infection and vaccination settings. Finally, we propose novel vaccine strategies that will harness the knowledge of protective immunity and employ new technology and vaccine concepts to inform next-generation HCMV vaccine development.

Subcellular organization is essential for life. Cells organize their functions into organelles to concentrate their machinery and supplies for optimal efficiency. Likewise, viruses organize their replication machinery into compartments or factories within their host cells for optimal replicative efficiency. In this review, we discuss how DNA viruses that infect both eukaryotic cells and bacteria assemble replication compartments for synthesis of progeny viral DNA and transcription of the viral genome. Eukaryotic DNA viruses assemble replication compartments in the nucleus of the host cell while DNA bacteriophages assemble compartments called phage nuclei in the bacterial cytoplasm. Thus, DNA viruses infecting host cells from different domains of life share common replication strategies.

Many viruses induce shutoff of host gene expression (host shutoff) as a strategy to take over cellular machinery and evade host immunity. Without host shutoff activity, these viruses generally replicate poorly in vivo, attesting to the importance of this antiviral strategy. In this review, we discuss one particularly advantageous way for viruses to induce host shutoff: triggering widespread host messenger RNA (mRNA) decay. Viruses can trigger increased mRNA destruction either directly, by encoding RNA cleaving or decapping enzymes, or indirectly, by activating cellular RNA degradation pathways. We review what is known about the mechanism of action of several viral RNA degradation factors. We then discuss the consequences of widespread RNA degradation on host gene expression and on the mechanisms of immune evasion, highlighting open questions. Answering these questions is critical to understanding how viral RNA degradation factors regulate host gene expression and how this process helps viruses evade host responses and replicate.

For decades, viruses have been isolated primarily from humans and other organisms. Interestingly, one of the most complex sides of the virosphere was discovered using free-living amoebae as hosts. The discovery of giant viruses in the early twenty-first century opened a new chapter in the field of virology. Giant viruses are included in the phylum Nucleocytoviricota and harbor large and complex DNA genomes (up to 2.7 Mb) encoding genes never before seen in the virosphere and presenting gigantic particles (up to 1.5 μm). Different amoebae have been used to isolate and characterize a plethora of new viruses with exciting details about novel viral biology. Through distinct isolation techniques and metagenomics, the diversity and complexity of giant viruses have astonished the scientific community. Here, we discuss the latest findings on amoeba viruses and how using these single-celled organisms as hosts has revealed entities that have remained hidden in plain sight for ages.

Advances in our understanding of prokaryotic antiphage defense mechanisms in the past few years have revealed a multitude of new cyclic nucleotide signaling molecules that play a crucial role in switching infected cells into an antiviral state. Defense pathways including type III CRISPR (clustered regularly interspaced palindromic repeats), CBASS (cyclic nucleotide-based antiphage signaling system), PYCSAR (pyrimidine cyclase system for antiphage resistance), and Thoeris all use cyclic nucleotides as second messengers to activate a diverse range of effector proteins. These effectors typically degrade or disrupt key cellular components such as nucleic acids, membranes, or metabolites, slowing down viral replication kinetics at great cost to the infected cell. Mechanisms to manipulate the levels of cyclic nucleotides are employed by cells to regulate defense pathways and by viruses to subvert them. Here we review the discovery and mechanism of the key pathways, signaling molecules and effectors, parallels and differences between the systems, open questions, and prospects for future research in this area.

Citrus tristeza virus (CTV) is the most destructive viral pathogen of citrus. During the past century, CTV induced grave epidemics in citrus-growing areas worldwide that have resulted in a loss of more than 100 million trees. At present, the virus continues to threaten citrus production in many different countries. Research on CTV is accompanied by distinctive challenges stemming from the large size of its RNA genome, the narrow host range limited to slow-growing Citrus species and relatives, and the complexity of CTV populations. Despite these hurdles, remarkable progress has been made in understanding the CTV-host interactions and in converting the virus into a tool for crop protection and improvement. This review focuses on recent advances that have shed light on the mechanisms underlying CTV infection. Understanding these mechanisms is pivotal for the development of means to control CTV diseases and, ultimately, turn this virus into an ally.

Herpesviruses are ancient large DNA viruses that have exploited gene capture as part of their strategy to escape immune surveillance, promote virus spreading, or reprogram host cells to benefit their survival. Most acquired genes are transmembrane proteins and cytokines, such as viral G protein-coupled receptors (vGPCRs), chemokines, and chemokine-binding proteins. This review focuses on the vGPCRs encoded by the human β- and γ-herpesviruses. These include receptors from human cytomegalovirus, which encodes four vGPCRs: US27, US28, UL33, and UL78; human herpesvirus 6 and 7 with two receptors: U12 and U51; Epstein-Barr virus with one: BILF1; and Kaposi's sarcoma-associated herpesvirus with one: open reading frame 74, ORF74. We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from endogenous receptors. Finally, we briefly discuss the therapeutic targeting of vGPCRs as future treatment of acute and chronic herpesvirus infections.