Abstract
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.
Highlights
De Novo Creation of GenesIn the majority of cases, new genes are created by transfer of existing genetic material [1]
Sera from 15 human immunodeficiency virus type 1 (HIV-1) patients were able to immunoprecipitate in vitro translated Antisense Protein (ASP); patients were at stage I, III and IV of infection during pre-HAART era Antibodies to ASP are detectable in serum of untreated patients, but not in serum of treated patients or in serum of HIV-1 controllers
When considering the small size and the complexity of the HIV-1 genome, and the intense immune pressure acting on the virus, it would seem highly unlikely that the asp gene appeared by chance, and that it would be conserved if it did not encode for a protein product, or that such a protein did not provide any selective advantage to the virus
Summary
In the majority of cases, new genes are created by transfer of existing genetic material [1]. De novo gene creation can occur in intergenic regions and introns [3,4], and in genomic regions that already contain a protein-coding gene—a process called ‘overprinting’ (Figure 1) In this case, a genomic region with an existing coding sequence in one of the six reading frames (Figure 1A) undergoes point mutations in one of the other five reading frames that generate a new start codon (Figure 1B) and/or remove stop codons (Figure 1C), giving rise to a second coding sequence. Showed that, in the case of overlapping pairs, the codon usage of ancestral genes is is more similar to the rest of the genome than that of novel genes [26]. There is evidence that creation of novel genes by overprinting allows viruses to make virtue out of necessity
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