Different HIV‐1 <i>env</i> frames: gp120 and ASP (antisense protein) biosynthesis, and theirs co‐variation tropic amino acid signatures in X4‐ and R5‐viruses

Dimonte, Salvatore

doi:10.1002/jmv.24611

Cited by 9 publications

(11 citation statements)

References 50 publications

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“…Altogether, this study strongly suggests that the asp gene which appeared concomitantly with, and is uniquely conserved within, the HIV-1 pandemic group M, is the 10th HIV-1 gene and that its transcriptional and/or translational products may endow the virus with an evolutionary advantage (Cassan et al, 2016). Of note, 1 year after this study, using an extensive sequence analysis (660 viral strains), another study found that asp mutations were associated with mutations of the hypervariable region V3 of env and thereby proposed that asp mutations could be linked to viral tropism and different co-receptor usage (Dimonte, 2017).…”

Section: Origin Evolution and Conservation Of The Asp Genementioning

confidence: 85%

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

et al. 2021

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It was first predicted in 1988 that there may be an Open Reading Frame (ORF) on the negative strand of the Human Immunodeficiency Virus type 1 (HIV-1) genome that could encode a protein named AntiSense Protein (ASP). In spite of some controversy, reports began to emerge some years later describing the detection of HIV-1 antisense transcripts, the presence of ASP in transfected and infected cells, and the existence of an immune response targeting ASP. Recently, it was established that the asp gene is exclusively conserved within the pandemic group M of HIV-1. In this review, we summarize the latest findings on HIV-1 antisense transcripts and ASP, and we discuss their potential functions in HIV-1 infection together with the role played by antisense transcripts and ASPs in some other viruses. Finally, we suggest pathways raised by the study of antisense transcripts and ASPs that may warrant exploration in the future.

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Section: Origin Evolution and Conservation Of The Asp Genementioning

confidence: 85%

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

et al. 2021

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“…Two subsequent reports analyzed co-evolution of the ASP and ENV open reading frames. Dimonte studied the correlation between mutations in ASP and ENV, and CCR5 vs. CXCR4 coreceptor usage [ 78 ]. The author first used the G2P algorithm to predict the tropism of ~24,000 HIV-1 subtype B env sequences deposited in the Los Alamos HIV Sequence Database, and then analyzed the association of mutations in ASP with predicted coreceptor usage.…”

Section: Origin Conservation and Evolution Of Aspmentioning

confidence: 99%

“…The gp120 V3 loop becomes exposed upon binding of gp120 with CD4, contacts the coreceptor (CCR5 or CXCR4), and mediated virus entry into the target cell [ 79 ]. The author found eight sites on ASP where specific mutations are associated in a statistically significant manner with mutations in the V3 loop of gp120 and with CCR5/CXCR4 tropism; six of these eight mutations map in the extracellular/viral loop of ASP [ 78 ]. It should be underscored that the ASP ORF overlaps the env gene in the region of the V4 and V5 loops, but not V3.…”

Section: Origin Conservation and Evolution Of Aspmentioning

confidence: 99%

The HIV-1 Antisense Gene ASP: The New Kid on the Block

Gholizadeh

Iqbal

et al. 2021

Vaccines

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Viruses have developed incredibly creative ways of making a virtue out of necessity, including taking full advantage of their small genomes. Indeed, viruses often encode multiple proteins within the same genomic region by using two or more reading frames in both orientations through a process called overprinting. Complex retroviruses provide compelling examples of that. The human immunodeficiency virus type 1 (HIV-1) genome expresses sixteen proteins from nine genes that are encoded in the three positive-sense reading frames. In addition, the genome of some HIV-1 strains contains a tenth gene in one of the negative-sense reading frames. The so-called Antisense Protein (ASP) gene overlaps the HIV-1 Rev Response Element (RRE) and the envelope glycoprotein gene, and encodes a highly hydrophobic protein of ~190 amino acids. Despite being identified over thirty years ago, relatively few studies have investigated the role that ASP may play in the virus lifecycle, and its expression in vivo is still questioned. Here we review the current knowledge about ASP, and we discuss some of the many unanswered questions.

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“…First, in a monumental study of approximately 23,000 HIV and SIV sequences, Cassan and colleagues convincingly showed that the ASP ORF is exclusively found in group M viruses and correlates with subtypes, or clades, responsible for the human pandemic [65]. Next, mutations in asp, not reflected in overlapping env sequences, are associated with CCR5 and CXCR4 tropism [66]. Finally, the effect of natural selection on asp as a functional gene was examined.…”

Section: Formulation Of the Hypothesis For An Hiv-1 Antisense Proteinmentioning

confidence: 99%

Retroviral Antisense Transcripts and Genes: 33 Years after First Predicted, a Silent Retroviral Revolution?

Miller

Zimmer

Moutot

et al. 2021

Viruses

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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 “contagium vivum fluidum”, 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 asp 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.

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Different HIV‐1 env frames: gp120 and ASP (antisense protein) biosynthesis, and theirs co‐variation tropic amino acid signatures in X4‐ and R5‐viruses

Cited by 9 publications

References 50 publications

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

The HIV-1 Antisense Gene ASP: The New Kid on the Block

Retroviral Antisense Transcripts and Genes: 33 Years after First Predicted, a Silent Retroviral Revolution?

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