Mosaic genome structure of simian immunodeficiency virus from West African green monkeys

Abstract

Elucidation of the phylogenetic origins of simian and human immunodeficiency viruses (SIV and HIV) is fundamental to the understanding of HIV pathogenesis and the spread of AIDS worldwide. In this study, we molecularly characterized multiple SIV(AGM) isolates from four different African green monkey species (vervet, grivet, sabaeus and tantalus monkeys). Phylogenetic analysis of partial (1 kb) env sequences indicated that all SIV(AGM) strains cluster together, and that they fall into four distinct sequence sub-groups according to their species of origin. However, alignment of long terminal repeat sequences revealed that SIVs from West African sabaeus monkeys contain a structural feature (a duplication of the transactivation response element) thus far only found in otherwise highly divergent lentiviruses infecting sooty mangabeys (SIV(SM)) and humans (HIV-2). To determine whether there were additional similarities with the SIV(SM)/HIV-2 group, a full-length replication competent sabaeus provirus was cloned and sequenced. In phylogenetic trees derived from the central and 3' coding regions, the sabaeus virus clustered with SIV(AGM) isolates from other African green monkey species. However, in trees derived from the 3' half of gag and the adjacent 5' region of pol, the sabaeus virus grouped with the SIV(SM)/HIV-2 lineage. These results indicated that the sabaeus virus comprised a mosaic genome which must have resulted from recombination of divergent lentiviruses in the distant past. A second, independent sabaeus isolate exhibited similar phylogenetic relationships, suggesting that all West African green monkey viruses share this complex evolutionary history. Taken together, these results indicate that African green monkeys have been infected with SIV(AGM) for very long periods of time, and that recombination and cross-species transmission in the wild have contributed to the genetic complexity of primate lentiviruses.