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Science (New York, N.Y.) Aug 2021Gag, the primary structural protein of HIV-1, is recruited to the plasma membrane for virus assembly by its matrix (MA) domain. Gag is subsequently cleaved into its...
Gag, the primary structural protein of HIV-1, is recruited to the plasma membrane for virus assembly by its matrix (MA) domain. Gag is subsequently cleaved into its component domains, causing structural maturation to repurpose the virion for cell entry. We determined the structure and arrangement of MA within immature and mature HIV-1 through cryo-electron tomography. We found that MA rearranges between two different hexameric lattices upon maturation. In mature HIV-1, a lipid extends out of the membrane to bind with a pocket in MA. Our data suggest that proteolytic maturation of HIV-1 not only assembles the viral capsid surrounding the genome but also repurposes the membrane-bound MA lattice for an entry or postentry function and results in the partial removal of up to 2500 lipids from the viral membrane.
Topics: Capsid; Electron Microscope Tomography; HIV Antigens; HIV-1; Lipid Bilayers; Membrane Lipids; Models, Molecular; Protein Conformation; Protein Domains; Protein Structure, Secondary; Viral Envelope; Virion; Virus Assembly; env Gene Products, Human Immunodeficiency Virus; gag Gene Products, Human Immunodeficiency Virus
PubMed: 34353956
DOI: 10.1126/science.abe6821 -
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 -
Frontiers in Plant Science 2020LTR-retrotransposons share a common genomic organization in which the 5' long terminal repeat (LTR) is followed by the and genes and terminates with the 3' LTR.... (Review)
Review
LTR-retrotransposons share a common genomic organization in which the 5' long terminal repeat (LTR) is followed by the and genes and terminates with the 3' LTR. Although GAG-POL-encoded proteins are considered sufficient to accomplish the LTR-retrotransposon transposition, a number of elements carrying additional open reading frames (aORF) have been described. In some cases, the presence of an aORF can be explained by a phenomenon similar to retrovirus gene transduction, but in these cases the aORFs are present in only one or a few copies. On the contrary, many elements contain aORFs, or derivatives, in all or most of their copies. These aORFs are more frequently located between and 3' LTR, and they could be in sense or antisense orientation with respect to -. Sense aORFs include those encoding for ENV-like proteins, so called because they have some structural and functional similarities with retroviral ENV proteins. Antisense aORFs between and 3' LTR are also relatively frequent and, for example, are present in some characterized LTR-retrotransposon families like maize Grande, rice RIRE2, or Retand, although their possible roles have been not yet determined. Here, we discuss the current knowledge about these sense and antisense aORFs in plant LTR-retrotransposons, suggesting their possible origins, evolutionary relevance, and function.
PubMed: 32528484
DOI: 10.3389/fpls.2020.00555 -
Viruses Mar 2022HIV-1 viral particle assembly occurs specifically at the plasma membrane and is driven primarily by the viral polyprotein Gag. Selective association of Gag with the... (Review)
Review
HIV-1 viral particle assembly occurs specifically at the plasma membrane and is driven primarily by the viral polyprotein Gag. Selective association of Gag with the plasma membrane is a key step in the viral assembly pathway, which is traditionally attributed to the MA domain. MA regulates specific plasma membrane binding through two primary mechanisms including: (1) specific interaction of the MA highly basic region (HBR) with the plasma membrane phospholipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P], and (2) tRNA binding to the MA HBR, which prevents Gag association with non-PI(4,5)P containing membranes. Gag multimerization, driven by both CA-CA inter-protein interactions and NC-RNA binding, also plays an essential role in viral particle assembly, mediating the establishment and growth of the immature Gag lattice on the plasma membrane. In addition to these functions, the multimerization of HIV-1 Gag has also been demonstrated to enhance its membrane binding activity through the MA domain. This review provides an overview of the mechanisms regulating Gag membrane binding through the MA domain and multimerization through the CA and NC domains, and examines how these two functions are intertwined, allowing for multimerization mediated enhancement of Gag membrane binding.
Topics: Cell Membrane; HIV-1; Membranes; Phosphatidylinositol 4,5-Diphosphate; Protein Binding; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 35337029
DOI: 10.3390/v14030622 -
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 Jul 2017Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing... (Review)
Review
Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three specialized non-Long Terminal Repeat (non-LTR) retrotransposons. These three very special retroelements transpose in head to tail arrays, always in the same orientation at the end of the chromosomes but never in interior locations. Apparently, retrotransposon and telomerase telomeres might seem very different, but a detailed view of their mechanisms reveals similarities explaining how the loss of telomerase in a Drosophila ancestor could successfully have been replaced by the telomere retrotransposons. In this review, we will discover that although HeT-A, TART, and TAHRE are still the only examples to date where their targeted transposition is perfectly tamed into the telomere biology of Drosophila, there are other examples of retrotransposons that manage to successfully integrate inside and at the end of telomeres. Because the aim of this special issue is viral integration at telomeres, understanding the base of the telomerase exceptions will help to obtain clues on similar strategies that mobile elements and viruses could have acquired in order to ensure their survival in the host genome.
Topics: Animals; Drosophila; Drosophila Proteins; Gene Products, gag; Retroelements; Telomere
PubMed: 28753967
DOI: 10.3390/v9070192 -
Viruses Sep 2016Human immunodeficiency virus type 1 (HIV-1) replication is a highly regulated process requiring the recruitment of viral and cellular components to the plasma membrane... (Review)
Review
Human immunodeficiency virus type 1 (HIV-1) replication is a highly regulated process requiring the recruitment of viral and cellular components to the plasma membrane for assembly into infectious particles. This review highlights the recent process of understanding the selection of the genomic RNA (gRNA) by the viral Pr55(Gag) precursor polyprotein, and the processes leading to its incorporation into viral particles.
Topics: HIV-1; Humans; Protein Binding; RNA, Viral; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 27626439
DOI: 10.3390/v8090248 -
Current Opinion in Virology Jun 2016Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the... (Review)
Review
Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered.
Topics: Capsid Proteins; HIV-1; Humans; Peptide Hydrolases; Proteolysis; Retroviridae; Viral Proteins; Virion; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 27010119
DOI: 10.1016/j.coviro.2016.02.008 -
Viruses Nov 2021HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for...
HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for virion infectivity. The precise stepwise nature of the packaging process has not been resolved. This is largely due to a prior lack of structural techniques that follow RNA structural changes within an RNA-protein complex. Here, we apply the in-gel SHAPE (selective 2'OH acylation analysed by primer extension) technique to study the initiation of HIV-1 packaging, examining the interaction between the packaging signal RNA and the Gag polyprotein, and compare it with that of the NC domain of Gag alone. Our results imply interactions between Gag and monomeric packaging signal RNA in switching the RNA conformation into a dimerisation-competent structure, and show that the Gag-dimer complex then continues to stabilise. These data provide a novel insight into how HIV-1 regulates the translation and packaging of its genome.
Topics: Genome, Viral; HIV Infections; HIV-1; Humans; Nucleic Acid Conformation; RNA, Viral; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 34960658
DOI: 10.3390/v13122389 -
AIDS Research and Therapy Sep 2023Human immunodeficiency virus type 1 (HIV-1) is the primary epidemic strain in China. Its genome contains two regulatory genes (tat and rev), three structural genes (gag,... (Review)
Review
Human immunodeficiency virus type 1 (HIV-1) is the primary epidemic strain in China. Its genome contains two regulatory genes (tat and rev), three structural genes (gag, pol, and env), and four accessory genes (nef, vpr, vpu, and vif). Long terminal repeats (LTRs) in thegenome regulate integration, duplication, and expression of viral gene. The permissibility of HIV-1 infection hinges on the host cell cycle status. HIV-1 replicates by exploiting various cellular processes via upregulation or downregulation of specific cellular proteins that also control viral pathogenesis. For example, HIV-1 regulates the life cycle of p53, which in turn contributes significantly to HIV-1 pathogenesis. In this article, we review the interaction between HIV-1-associated factors and p53, providing information on their regulatory and molecular mechanisms, hinting possible directions for further research.
Topics: Humans; HIV-1; Tumor Suppressor Protein p53; HIV Infections; China; Genes, Viral
PubMed: 37691100
DOI: 10.1186/s12981-023-00563-7