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Science China. Life Sciences Feb 2022Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world. SARS-CoV-2 is an enveloped, plus-stranded RNA virus with a... (Review)
Review
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world. SARS-CoV-2 is an enveloped, plus-stranded RNA virus with a single-stranded RNA genome of approximately 30,000 nucleotides. The SARS-CoV-2 genome encodes 29 proteins, including 16 nonstructural, 4 structural and 9 accessory proteins. To date, over 1,228 experimental structures of SARS-CoV-2 proteins have been deposited in the Protein Data Bank (PDB), including 16 protein structures, two functional domain structures of nucleocapsid (N) protein, and scores of complexes. Overall, they exhibit high similarity to SARS-CoV proteins. Here, we summarize the progress of structural and functional research on SARS-CoV-2 proteins. These studies provide structural and functional insights into proteins of SARS-CoV-2, and further elucidate the daedal relationship between different components at the atomic level in the viral life cycle, including attachment to the host cell, viral genome replication and transcription, genome packaging and assembly, and virus release. It is important to understand the structural and functional properties of SARS-CoV-2 proteins as it will facilitate the development of anti-CoV drugs and vaccines to prevent and control the current SARS-CoV-2 pandemic.
Topics: COVID-19; Genome, Viral; Humans; Protein Conformation; SARS-CoV-2; Transcription, Genetic; Viral Proteins; Virus Assembly; Virus Replication
PubMed: 34387838
DOI: 10.1007/s11427-021-1964-4 -
Cell Oct 2020SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed...
SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.
Topics: Animals; Betacoronavirus; Chlorocebus aethiops; Cryoelectron Microscopy; Humans; Mass Spectrometry; Models, Molecular; Protein Conformation; SARS-CoV-2; Vero Cells; Viral Proteins; Virus Assembly; Virus Cultivation
PubMed: 32979942
DOI: 10.1016/j.cell.2020.09.018 -
Autophagy Jul 2022Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.
Topics: Autophagy; Humans; Orthobunyavirus; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Virus Assembly
PubMed: 34747299
DOI: 10.1080/15548627.2021.1994296 -
Viruses Feb 2022The assembly of HIV-1 particles is a concerted and dynamic process that takes place on the plasma membrane of infected cells. An abundance of recent discoveries has... (Review)
Review
The assembly of HIV-1 particles is a concerted and dynamic process that takes place on the plasma membrane of infected cells. An abundance of recent discoveries has advanced our understanding of the complex sequence of events leading to HIV-1 particle assembly, budding, and release. Structural studies have illuminated key features of assembly and maturation, including the dramatic structural transition that occurs between the immature Gag lattice and the formation of the mature viral capsid core. The critical role of inositol hexakisphosphate (IP6) in the assembly of both the immature and mature Gag lattice has been elucidated. The structural basis for selective packaging of genomic RNA into virions has been revealed. This review will provide an overview of the HIV-1 assembly process, with a focus on recent advances in the field, and will point out areas where questions remain that can benefit from future investigation.
Topics: HIV-1; Virion; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 35336885
DOI: 10.3390/v14030478 -
The Journal of General Virology Apr 2023Unlike many segmented negative-sense RNA viruses, most members of the bud at Golgi membranes, as opposed to the plasma membrane. Central players in this assembly... (Review)
Review
Unlike many segmented negative-sense RNA viruses, most members of the bud at Golgi membranes, as opposed to the plasma membrane. Central players in this assembly process are the envelope glycoproteins, Gn and Gc, which upon translation undergo proteolytic processing, glycosylation and trafficking to the Golgi, where they interact with ribonucleoprotein genome segments and bud into Golgi-derived compartments. The processes involved in genome packaging during virion assembly can lead to the generation of reassorted viruses, if a cell is co-infected with two different bunyaviruses, due to mismatching of viral genome segment packaging. This can lead to viruses with high pathogenic potential, as demonstrated by the emergence of Schmallenberg virus. This review focuses on the assembly pathways of tri-segmented bunyaviruses, highlighting some areas in need of further research to understand these important pathogens with zoonotic potential.
Topics: Orthobunyavirus; RNA Viruses; Glycosylation; Virus Assembly
PubMed: 37083579
DOI: 10.1099/jgv.0.001845 -
Nature Microbiology Aug 2022
Topics: Chikungunya Fever; Chikungunya virus; Humans; Virus Assembly
PubMed: 35918424
DOI: 10.1038/s41564-022-01190-0 -
Viruses May 2022Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles.... (Review)
Review
Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.
Topics: Genomics; HIV-1; Humans; RNA, Viral; Retroviridae; Virus Assembly
PubMed: 35632835
DOI: 10.3390/v14051094 -
Trends in Microbiology Aug 2019Successful replication of the AIDS retrovirus, HIV, requires that its genomic RNA be packaged in assembling virus particles with high fidelity. However, cellular mRNAs... (Review)
Review
Successful replication of the AIDS retrovirus, HIV, requires that its genomic RNA be packaged in assembling virus particles with high fidelity. However, cellular mRNAs can also be packaged under some conditions. Viral RNA (vRNA) contains a 'packaging signal' (ψ) and is packaged as a dimer, with two vRNA monomers joined by a limited number of base pairs. It has two conformers, only one of which is capable of dimerization and packaging. Recent years have seen important progress on the 3D structure of dimeric ψ. Gag, the protein that assembles into the virus particle, interacts specifically with ψ, but this is obscured under physiological conditions by its high nonspecific affinity for any RNA. New results suggest that vRNA is selected for packaging because ψ nucleates assembly more efficiently than other RNAs.
Topics: HIV-1; Humans; RNA, Viral; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 31085095
DOI: 10.1016/j.tim.2019.04.003 -
Viruses Mar 2021The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and... (Review)
Review
The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Humans; RNA, Viral; Viral Nonstructural Proteins; Virus Assembly; Virus Replication
PubMed: 33809897
DOI: 10.3390/v13030520 -
Virology Nov 2019RNA viruses carry out selective packaging of their genomes in a variety of ways, many involving a genomic packaging signal. The first coronavirus packaging signal was... (Review)
Review
RNA viruses carry out selective packaging of their genomes in a variety of ways, many involving a genomic packaging signal. The first coronavirus packaging signal was discovered nearly thirty years ago, but how it functions remains incompletely understood. This review addresses the current state of knowledge of coronavirus genome packaging, which has mainly been studied in two prototype species, mouse hepatitis virus and transmissible gastroenteritis virus. Despite the progress that has been made in the mapping and characterization of some packaging signals, there is conflicting evidence as to whether the viral nucleocapsid protein or the membrane protein plays the primary role in packaging signal recognition. The different models for the mechanism of genomic RNA packaging that have been prompted by these competing views are described. Also discussed is the recent exciting discovery that selective coronavirus genome packaging is critical for in vivo evasion of the host innate immune response.
Topics: Models, Biological; Murine hepatitis virus; Nucleocapsid Proteins; RNA, Viral; Transmissible gastroenteritis virus; Viral Matrix Proteins; Virus Assembly
PubMed: 31505321
DOI: 10.1016/j.virol.2019.08.031