Absence of accessory genes in a divergent simian T-lymphotropic virus type 1 isolated from a bonnet macaque (Macaca radiata)

Abstract

Background: Primate T-lymphotropic viruses type 1 (PTLV-1) are complex retroviruses infecting both human (HTLV-1) and simian (STLV-1) hosts. They share common epidemiological, clinical and molecular features. In addition to the canonical gag, pol, env retroviral genes, PTLV-1 purportedly encodes regulatory (i.e. Tax, Rex, and HBZ) and accessory proteins (i.e. P12/8, P13, P30). The latter have been found essential for viral persistence in vivo.

Methodology/principal findings: We have isolated a STLV-1 virus from a bonnet macaque (Macaca radiata-Mra18C9), a monkey from India. The complete sequence was obtained and phylogenetic analyses were performed. The Mra18C9 strain is highly divergent from the known PTLV-1 strains. Intriguingly, the Mra18C9 lacks the 3 accessory open reading frames. In order to determine if the absence of accessory proteins is specific to this particular strain, a comprehensive analysis of the complete PTLV-1 genomes available in Genbank was performed and found that the lack of one or many accessory ORF is common among PTLV-1.

Conclusion: This study raises many questions regarding the actual nature, role and importance of accessory proteins in the PTLV-1 biology.

Fig 1. Genomic organization of STLV-1 Mra18C9.

Nucleotide numbering of splicing sites and initiation/stop codon are according to the Mra18C9 proviral genome. The upper boxes represent the LTRs. The other boxes represent the ORFs. * indicate the frame-shifting sites.

Fig 2. Phylogenetic analyses of the MraC18C9 STLV-1 strain.

The presented phylogenetic trees were all generated by a Bayesian approach. The scale bar represents nucleotide substitutions per site. Values correspond to posterior probabilities. A—Phylogenetic tree generated by a Bayesian approach using a concatenation of gag-pol-env-tax genes (alignment of 5820 nucleotides). PTLV-4 sequences (GabL14, Ggo51461 and Ggo 50539) were used as outgroup. B—Phylogenetic tree generated using the LTR sequence (alignment of 701 nucleotides). The tree is unrooted and comprises most PTLV-1 complete LTR sequences available. C- Phylogenetic tree using an alignment of an env gene fragment of 483 nucleotides. The tree is unrooted and comprises most PTLV-1 env sequences available. The denomination African PTLV-1 comprises HTLV-1a, and PTLV-1b, d, e, f, and g strains. MM stands for Macaca maura; MMU stands for M. mulatta; MFA stands for M. fascicularis; MAC and mar stand for Macaca arctoides; TE stands for M. tonkeana; HS stands for Hylobates syndactylus; Ou stands for Orangutan; Mra stands for M.radiata; Cxxx strains were isolated from Hylobates pileatus.