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Viruses Nov 2021Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been... (Review)
Review
Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been especially true in the field of virology, where the discovery of a "", or infectious fluid remaining after excluding bacteria by filtration, was initially ignored because it did not coincide with the established view of microorganisms. Subsequent studies on such infectious agents, eventually termed "viruses", were met with skepticism. However, after an abundance of proof accumulated, viruses were eventually acknowledged as defined microbiological entities. Next, the proposed role of viruses in oncogenesis in animals was disputed, as was the unique mechanism of genome replication by reverse transcription of RNA by the retroviruses. This same pattern of skepticism holds true for the prediction of the existence of retroviral "antisense" transcripts and genes. From the time of their discovery, it was thought that retroviruses encoded proteins on only one strand of proviral DNA. However, in 1988, it was predicted that human immunodeficiency virus type 1 (HIV-1), and other retroviruses, express an antisense protein encoded on the DNA strand opposite that encoding the known viral proteins. Confirmation came quickly with the characterization of the antisense protein, HBZ, of the human T-cell leukemia virus type 1 (HTLV-1), and the finding that both the protein and its antisense mRNA transcript play key roles in viral replication and pathogenesis. However, acceptance of the existence, and potential importance, of a corresponding antisense transcript and protein (ASP) in HIV-1 infection and pathogenesis has lagged, despite gradually accumulating theoretical and experimental evidence. The most striking theoretical evidence is the finding that is highly conserved in group M viruses and correlates exclusively with subtypes, or clades, responsible for the AIDS pandemic. This review outlines the history of the major shifts in thought pertaining to the nature and characteristics of viruses, and in particular retroviruses, and details the development of the hypothesis that retroviral antisense transcripts and genes exist. We conclude that there is a need to accelerate studies on ASP, and its transcript(s), with the view that both may be important, and overlooked, targets in anti-HIV therapeutic and vaccine strategies.
Topics: Carcinogenesis; Genome, Viral; HIV-1; History, 20th Century; History, 21st Century; Human Immunodeficiency Virus Proteins; Human T-lymphotropic virus 1; Humans; Open Reading Frames; RNA, Antisense; RNA, Messenger; Retroviridae; Retroviridae Proteins; Transcription, Genetic; Viral Envelope Proteins; Virology; Virus Replication
PubMed: 34835027
DOI: 10.3390/v13112221 -
Uirusu 2014Location of virus assembly in infected cells has major influences on efficiencies of virus assembly and release and on post-assembly processes including cell-to-cell... (Review)
Review
Location of virus assembly in infected cells has major influences on efficiencies of virus assembly and release and on post-assembly processes including cell-to-cell transmission. Therefore, for better understanding of virus spread and for developing new antiviral strategies, it is important to elucidate mechanisms by which the subcellular site of virus particle assembly is determined. Retrovirus particle assembly is driven by viral structural protein Gag. In the case of HIV-1, Gag binds to the plasma membrane (PM) via the N-terminal MA domain and forms nascent particles at this location. Recent studies reveled that PM-specific phospholipid PI(4,5)P2 plays an important role in directing Gag to the PM through its interaction with MA. In this review, I will summarize our current understanding of relationships between retroviral MA domains and phospholipids in cellular membranes and discuss possible mechanisms by which lipids and other factors regulate membrane binding and subcellular localization of retroviral Gag proteins.
Topics: Antiviral Agents; Cell Membrane; Drug Discovery; Gene Products, gag; HIV-1; Phosphatidylinositols; Protein Binding; Protein Structure, Tertiary; Retroviridae; Viral Proteins; Virus Assembly
PubMed: 26437838
DOI: 10.2222/jsv.64.155 -
Retrovirology Nov 2006In recognition of the growing influence of cell biology in retrovirus research, we recently organized a Summer conference sponsored by the American Society for Cell... (Review)
Review
In recognition of the growing influence of cell biology in retrovirus research, we recently organized a Summer conference sponsored by the American Society for Cell Biology (ASCB) on the Cell Biology of HIV-1 and other Retroviruses (July 20-23, 2006, Emory University, Atlanta, Georgia). The meeting brought together a number of leading investigators interested in the interplay between cell biology and retrovirology with an emphasis on presentation of new and unpublished data. The conference was arranged from early to late events in the virus replication cycle, with sessions on viral fusion, entry, and transmission; post-entry restrictions to retroviral infection; nuclear import and integration; gene expression/regulation of retroviral Gag and genomic RNA; and assembly/release. In this review, we will attempt to touch briefly on some of the highlights of the conference, and will emphasize themes and trends that emerged at the meeting. MEETING REPORT: The conference began with a keynote address from W. Sundquist on the biochemistry of HIV-1 budding. This presentation will be described in the section on Assembly and Release of Retroviruses.
Topics: Animals; Cattle; Gene Expression Regulation, Viral; HIV-1; Humans; Proteins; Retroviridae; Viral Proteins; Virus Replication
PubMed: 17083721
DOI: 10.1186/1742-4690-3-77 -
Retrovirology Oct 2006When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed... (Review)
Review
When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated.
Topics: Animals; Endogenous Retroviruses; Evolution, Molecular; History, 20th Century; Humans; Mammals; Mice; Phylogeny; Proviruses; Retroviridae; Virology
PubMed: 17018135
DOI: 10.1186/1742-4690-3-67 -
Genome Biology and Evolution Jan 2023Koala populations show marked differences in inbreeding levels and in the presence or absence of the endogenous Koala retrovirus (KoRV). These genetic differences among...
Koala populations show marked differences in inbreeding levels and in the presence or absence of the endogenous Koala retrovirus (KoRV). These genetic differences among populations may lead to severe disease impacts threatening koala population viability. In addition, the recent colonization of the koala genome by KoRV provides a unique opportunity to study the process of retroviral adaptation to vertebrate genomes and the impact this has on speciation, genome structure, and function. The genome build described here is from an animal from the bottlenecked Southern population free of endogenous and exogenous KoRV. It provides a more contiguous genome build than the previous koala reference derived from an animal from a more outbred Northern population and is the first koala genome from a KoRV polymerase-free animal.
Topics: Animals; Phascolarctidae; Australia; Retroviridae Infections; Retroviridae; Gammaretrovirus; Endogenous Retroviruses
PubMed: 36542479
DOI: 10.1093/gbe/evac176 -
Viruses Aug 2019Foamy viruses (FV) are retroviruses belonging to the subfamily. They are non-pathogenic viruses endemic in several mammalian hosts like non-human primates, felines,... (Review)
Review
Foamy viruses (FV) are retroviruses belonging to the subfamily. They are non-pathogenic viruses endemic in several mammalian hosts like non-human primates, felines, bovines, and equines. Retroviral DNA integration is a mandatory step and constitutes a prime target for antiretroviral therapy. This activity, conserved among retroviruses and long terminal repeat (LTR) retrotransposons, involves a viral nucleoprotein complex called intasome. In the last decade, a plethora of structural insights on retroviral DNA integration arose from the study of FV. Here, we review the biochemistry and the structural features of the FV integration apparatus and will also discuss the mechanism of action of strand transfer inhibitors.
Topics: Animals; Anti-Retroviral Agents; Catalytic Domain; DNA, Viral; HIV Infections; HIV-1; Humans; Integrase Inhibitors; Integrases; Models, Molecular; Nucleoproteins; Retroviridae; Spumavirus; Terminal Repeat Sequences; Virus Integration
PubMed: 31443391
DOI: 10.3390/v11090770 -
Uirusu Dec 2009Diseases caused by animal retroviruses have been recognized since 19th century in veterinary field. Most livestock and companion animals have own retroviruses. To... (Review)
Review
Diseases caused by animal retroviruses have been recognized since 19th century in veterinary field. Most livestock and companion animals have own retroviruses. To disclose the receptors for these retroviruses will be useful for understanding retroviral pathogenesis, developments of anti-retroviral drugs and vectors for human and animal gene therapies. Of retroviruses in veterinary field, receptors for the following viruses have been identified; equine infectious anemia virus, feline immunodeficiency virus, feline leukemia virus subgroups A, B, C, and T, Jaagsiekte sheep retrovirus, enzootic nasal tumor virus, avian leukosis virus subgroups A, B, C, D, E, and J, reticuloendotheliosis virus, RD-114 virus (a feline endogenous retrovirus), and porcine endogenous retrovirus subgroup A. Primate lentiviruses require two molecules (CD4 and chemokine receptors such as CXCR4) as receptors. Likewise, feline immunodeficiency virus also requires two molecules, i.e., CD134 (an activation marker of CD4 T cells) and CXCR4 in infection. Gammaretroviruses utilize multi-spanning transmembrane proteins, most of which are transporters of amino acids, vitamins and inorganic ions. Betaretroviruses and alpharetroviruses utilize transmembrane and/or GPI-anchored proteins as receptors. In this review, I overviewed receptors for animal retroviruses in veterinary field.
Topics: Animals; Cats; Endocytosis; Humans; Membrane Fusion; Mice; Receptors, Virus; Retroviridae; Retroviridae Infections; Sheep; Veterinary Medicine
PubMed: 20218331
DOI: 10.2222/jsv.59.223 -
Viruses May 2021Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to... (Review)
Review
Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for inappropriate gene products that cause/may cause diseases. Both these types of therapy have been used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy, immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference, clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases (TALENs) and custom treatment for Epstein-Barr virus, human T-lymphotropic virus 1, hepatitis B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi's sarcoma, Merkel cell polyomavirus, and cytomegalovirus.
Topics: Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Genetic Therapy; Humans; Immunotherapy; Retroviridae; Retroviridae Infections
PubMed: 34063186
DOI: 10.3390/v13050822 -
Viruses Sep 2011With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic... (Review)
Review
With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment, and vaccine development.
Topics: DNA Replication; DNA, Viral; Genetic Variation; Genome, Viral; HIV Infections; HIV-1; Humans; Mutation Rate; RNA, Viral; Recombination, Genetic; Retroviridae; Virus Replication
PubMed: 21994801
DOI: 10.3390/v3091650 -
Retrovirology Feb 2018Cryo-electron microscopy has undergone a revolution in recent years and it has contributed significantly to a number of different areas in biological research. In this... (Review)
Review
Cryo-electron microscopy has undergone a revolution in recent years and it has contributed significantly to a number of different areas in biological research. In this manuscript, we will describe some of the recent advancements in cryo-electron microscopy focussing on the advantages that this technique can bring rather than on the technology. We will then conclude discussing how the field of retrovirology has benefited from cryo-electron microscopy.
Topics: Animals; Cryoelectron Microscopy; Humans; Imaging, Three-Dimensional; Retroviridae; Virion
PubMed: 29471854
DOI: 10.1186/s12977-018-0405-6