A Challenge to the Ancient Origin of SIVagm Based on African Green Monkey Mitochondrial Genomes

Abstract

While the circumstances surrounding the origin and spread of HIV are becoming clearer, the particulars of the origin of simian immunodeficiency virus (SIV) are still unknown. Specifically, the age of SIV, whether it is an ancient or recent infection, has not been resolved. Although many instances of cross-species transmission of SIV have been documented, the similarity between the African green monkey (AGM) and SIVagm phylogenies has long been held as suggestive of ancient codivergence between SIVs and their primate hosts. Here, we present well-resolved phylogenies based on full-length AGM mitochondrial genomes and seven previously published SIVagm genomes; these allowed us to perform the first rigorous phylogenetic test to our knowledge of the hypothesis that SIVagm codiverged with the AGMs. Using the Shimodaira–Hasegawa test, we show that the AGM mitochondrial genomes and SIVagm did not evolve along the same topology. Furthermore, we demonstrate that the SIVagm topology can be explained by a pattern of west-to-east transmission of the virus across existing AGM geographic ranges. Using a relaxed molecular clock, we also provide a date for the most recent common ancestor of the AGMs at approximately 3 million years ago. This study substantially weakens the theory of ancient SIV infection followed by codivergence with its primate hosts. Elucidating the factors that influence the emergence of viral pathogens is of great importance to the study of infectious disease. HIV is understood to have originated from simian immunodeficiency viruses (SIVs) infecting nonhuman African primates, but the length of time the virus has been present in these apes and monkeys is not known. These infected primates do not normally develop immunodeficiency, and understanding the age of SIV might help explain why. It has been suggested that some of these monkeys have been infected for millions of years, because many closely related monkey species are infected with closely related viruses. One of the most prominent examples of this relationship is between the African green monkeys and their SIVs. In this study, we compared viral phylogenetic trees to those of their hosts' mitochondrial genomes and found that they do not support the theory of ancient infection followed by codivergence. Our results suggest that SIV did not infect these monkeys until after speciation and subsequently swept across their geographical ranges. If this infection is relatively recent, then avirulence may have evolved over a shorter time frame than previously suggested. This finding could have implications for the future trajectory of HIV disease severity.