SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations

• DOI: 10.1371/journal.ppat.1003011
• Publication Date: 2013-01-17T16:51:16Z
• Authors: Dongzhu Ma; Anna Jasinska; Jan Kristoff; J. Paul Grobler; Trudy Turner; Yoon Jung; Christopher Schmitt; Kevin Raehtz; Felix Feyertag; Natalie Martinez ...; Viskam Wijewardana; Donald S. Burke; David L. Robertson; Russell Tracy; Ivona Pandrea; Nelson Freimer; Cristian Apetrei
• Keywords: Male; Simian Acquired Immunodeficiency Syndrome; Genetic diversity; In-vivo replication; South Africa; Mutation Rate; Chlorocebus aethiops; Viral replication; Mangabeys Cercocebus-atys; Biology (General); Repetitive sequences; Recombination, Genetic; 0303 health sciences; Nonhuman primate hosts; Simian immunodeficiency virus; Medical microbiology; Molecular characterization; 3. Good health; Host-Pathogen Interactions; Female; Simian Immunodeficiency Virus; International Vervet Research Consortium; Sooty mangabeys; Research Article; Evolution; QH301-705.5; Mutation rate; Immunology; Molecular Sequence Data; Microbiology; Cercopithecus aethiops; Evolution, Molecular; 03 medical and health sciences; CD4(+) T-cells; Molecular sequence data; Virology; Animals; molecular; Genetic variation; Repetitive Sequences, Nucleic Acid; Host-pathogen interactions; Base Sequence; Genetic Variation; RC581-607; Base sequence; Recombination; Life sciences & biomedicine; Mandrillus-sphinx; nucleic acid; Parasitology; genetic; Immunologic diseases. Allergy; Science & technology

Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 10(4)-10(6) RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (10(7)-10(8) RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts.