Abstract
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.
Highlights
The first hypothesis on the existence of the asp gene overlapping env in the -2 frame on the antisense strand of Human Immunodeficiency Virus type 1 (HIV-1) proviral genome was formulated in 1988 (Miller, 1988; Figure 1)
The AntiSense Protein (ASP) Open Reading Frame (ORF) was detected in sequences of the most prevalent HIV-1 subtypes and circulating recombinant forms (CRFs) of the group M, while it was not observed in sequences from the endemic O group or in the rare N and P groups (Cassan et al, 2016). These results indicated that the creation of asp was concomitant with the emergence of the group M in humans
Future studies performed in HIV-1-infected cells will be determinant to exclude the possibility that ASP multimerization is a side effect of its overexpression in mammalian cells
Summary
The first hypothesis on the existence of the asp gene overlapping env in the -2 frame on the antisense strand of HIV-1 proviral genome was formulated in 1988 (Miller, 1988; Figure 1). An antisense gene was characterized in the genome of the Simian T-Leukemia Virus type 1 (STLV-1), and antisense transcripts were characterized in STLV-1-infected cells (Miura et al, 2013). The presence of antisense transcripts was first observed in an HIV-1-infected cell line in 1990 (Bukrinsky and Etkin, 1990), and ASP itself was first detected in 1995 (VanhéeBrossollet et al, 1995) Despite this promising discovery, very few studies were published on the investigation of ASP and its potential antisense transcripts. The presence of ASP-specific antibodies was detected in the plasma of HIV-1-infected individuals (Savoret et al, 2020), thereby confirming the pioneer study of Vanhée-Brossollet et al which first proposed the existence of ASP-specific antibodies (Vanhée-Brossollet et al, 1995), and further suggesting that ASP is expressed and immunogenic in vivo
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