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Journal of Molecular Biology Aug 2023Viruses are obligate parasites that rely on their host's cellular machinery for replication. To facilitate their replication cycle, many viruses have been shown to... (Review)
Review
Viruses are obligate parasites that rely on their host's cellular machinery for replication. To facilitate their replication cycle, many viruses have been shown to remodel the cellular architecture by inducing the formation of membraneless organelles (MLOs). Eukaryotic cells have evolved MLOs that are highly dynamic, self-organizing microenvironments that segregate biological processes and increase the efficiency of reactions by concentrating enzymes and substrates. In the context of viral infections, MLOs can be utilized by viruses to complete their replication cycle. This review focuses on the pathway used by the HIV-1 virus to remodel the nuclear landscape of its host, creating viral/host niches that enable efficient viral replication. Specifically, we discuss how the interaction between the HIV-1 capsid and the cellular factor CPSF6 triggers the formation of nuclear MLOs that support nuclear reverse transcription and viral integration in favored regions of the host chromatin. This review compiles current knowledge on the origin of nuclear HIV-MLOs and their role in early post-nuclear entry steps of the HIV-1 replication cycle.
Topics: Humans; Capsid; Capsid Proteins; Cell Nucleus; Chromatin; HIV Infections; Virus Replication; Biomolecular Condensates; HIV-1; mRNA Cleavage and Polyadenylation Factors; Host-Pathogen Interactions
PubMed: 37061085
DOI: 10.1016/j.jmb.2023.168094 -
Viruses Apr 2024Inflammation is a protective host response essential for controlling viral replication and promoting tissue repair [...].
Inflammation is a protective host response essential for controlling viral replication and promoting tissue repair [...].
Topics: Inflammation; Humans; Virus Diseases; Animals; Viruses; Virus Replication; Host-Pathogen Interactions
PubMed: 38675930
DOI: 10.3390/v16040588 -
Journal of Virology Jan 2024In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight...
In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.
Topics: Humans; Containment of Biohazards; COVID-19; United States; Viruses; Virology; Biomedical Research
PubMed: 38168672
DOI: 10.1128/jvi.01791-23 -
Nature Jan 2024Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation. Gabija is one of the most prevalent anti-phage...
Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation. Gabija is one of the most prevalent anti-phage defence systems, occurring in more than 15% of all sequenced bacterial and archaeal genomes, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-electron microscopy (cryo-EM) to define how Gabija proteins assemble into a supramolecular complex of around 500 kDa that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defence complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajA-GajB assembly (hereafter, GajAB) that is essential for phage resistance in vivo. We show that a phage-encoded protein, Gabija anti-defence 1 (Gad1), directly binds to the Gabija GajAB complex and inactivates defence. A cryo-EM structure of the virally inhibited state shows that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defence complex and define a unique mechanism of viral immune evasion.
Topics: Bacteria; Bacterial Proteins; Bacteriophages; Cryoelectron Microscopy; Crystallography, X-Ray; Deoxyribonucleases; DNA, Viral; Immune Evasion; Protein Multimerization
PubMed: 37992757
DOI: 10.1038/s41586-023-06855-2 -
Viruses Dec 2023Norway is situated in a remote and sparsely inhabited part of the world with about 5 [...].
Norway is situated in a remote and sparsely inhabited part of the world with about 5 [...].
Topics: Norway; Virology
PubMed: 38140624
DOI: 10.3390/v15122383 -
Advances in Experimental Medicine and... 2024Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral... (Review)
Review
Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.
Topics: Humans; Animals; Poxviridae Infections; Antiviral Agents; Pneumonia, Viral; Poxviridae; Vaccinia virus; Smallpox; Variola virus
PubMed: 38801579
DOI: 10.1007/978-3-031-57165-7_12 -
Seminars in Cell & Developmental Biology Sep 2023Viruses have evolved a multitude of mechanisms to combat barriers to productive infection in the host cell. Virally-encoded miRNAs are one such means to regulate host... (Review)
Review
Viruses have evolved a multitude of mechanisms to combat barriers to productive infection in the host cell. Virally-encoded miRNAs are one such means to regulate host gene expression in ways that benefit the virus lifecycle. miRNAs are small non-coding RNAs that regulate protein expression but do not trigger the adaptive immune response, making them powerful tools encoded by viruses to regulate cellular processes. Diverse viruses encode for miRNAs but little sequence homology exists between miRNAs of different viral species. Despite this, common cellular pathways are targeted for regulation, including apoptosis, immune evasion, cell growth and differentiation. Herein we will highlight the viruses that encode miRNAs and provide mechanistic insight into how viral miRNAs aid in lytic and latent infection by targeting common cellular processes. We also highlight how viral miRNAs can mimic host cell miRNAs as well as how viral miRNAs have evolved to regulate host miRNA expression. These studies dispel the myth that viral miRNAs are subtle regulators of gene expression, and highlight the critical importance of viral miRNAs to the virus lifecycle.
Topics: MicroRNAs; Viruses; Cell Differentiation; Protein Processing, Post-Translational; Gene Expression; Gene Expression Regulation, Viral; Gene Expression Regulation
PubMed: 36463091
DOI: 10.1016/j.semcdb.2022.11.007 -
Experimental & Molecular Medicine Apr 2024The dynamic spatial organization of genomes across time, referred to as the four-dimensional nucleome (4DN), is a key component of gene regulation and biological fate.... (Review)
Review
The dynamic spatial organization of genomes across time, referred to as the four-dimensional nucleome (4DN), is a key component of gene regulation and biological fate. Viral infections can lead to a reconfiguration of viral and host genomes, impacting gene expression, replication, latency, and oncogenic transformation. This review provides a summary of recent research employing three-dimensional genomic methods such as Hi-C, 4C, ChIA-PET, and HiChIP in virology. We review how viruses induce changes in gene loop formation between regulatory elements, modify chromatin accessibility, and trigger shifts between A and B compartments in the host genome. We highlight the central role of cellular chromatin organizing factors, such as CTCF and cohesin, that reshape the 3D structure of both viral and cellular genomes. We consider how viral episomes, viral proteins, and viral integration sites can alter the host epigenome and how host cell type and conditions determine viral epigenomes. This review consolidates current knowledge of the diverse host-viral interactions that impact the 4DN.
Topics: Humans; Genome, Viral; Animals; Host-Pathogen Interactions; Viruses; Chromatin; Virus Diseases
PubMed: 38658699
DOI: 10.1038/s12276-024-01207-0