Role of HIV RNA structure in recombination and speciation: romping in purine A, keeps HTLV away

TL;DR

This paper explores how differences in RNA nucleotide composition, especially purine and pyrimidine content, influence viral recombination and speciation, focusing on HIV-1 and HTLV-1 evolution within human hosts.

Contribution

It proposes that nucleotide composition differences in HIV-1 and HTLV-1 RNA genomes serve as a reproductive barrier, driving viral speciation by affecting RNA structure and recombination.

Findings

HIV-1 is enriched for purine A, reducing RNA kissing interactions.

HTLV-1 is enriched for pyrimidine C, diverging from HIV-1.

Nucleotide composition differences impair recombination, promoting speciation.

Abstract

Extreme enrichment of the human immunodeficiency virus (HIV-1) RNA genome for the purine A parallels the mild purine-loading of the RNAs of most organisms. This should militate against loop-loop "kissing" interactions between the structured viral genome and structured host RNAs, which can generate segments of double-stranded RNA sufficient to trigger intracellular alarms. However, human T cell leukaemia virus (HTLV-1), with the potential to invade the same host cell, shows extreme enrichment for the pyrimidine C. Assuming the low GC% HIV and the high GC% HTLV-1 to share a common ancestor, it was postulated that differences in GC% arose to prevent homologous recombination between these emerging lentiviral species. Sympatrically isolated by this intracellular reproductive barrier, prototypic HIV-1 seized the AU-rich (low GC%) high ground (thus committing to purine A rather than purine G). Prototypic HTLV-1 forwent this advantage and evolved an independent evolutionary strategy. Evidence supporting this hypothesis since its elaboration in the 1990s is growing. The conflict between the needs to encode accurately both a protein, and nucleic acid structure, is often resolved in favour of the nucleic acid because, apart from regulatory roles, structure is critical for recombination. However, above a sequence difference threshold, structure (and hence recombination) is impaired. New species can then arise.