Abstract
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 104–106 RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (107–108 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.
Highlights
Over 40 African nonhuman primate (NHP) species are naturally infected with simian immunodeficiency viruses (SIVs) [1,2,3]
We report that African green monkeys (AGMs) have likely been infected with SIVagm for a long period, ranging from the time of their speciation to Plio-Pleistocene migrations, refuting previous molecular clock calculations suggesting SIVagm to be of recent occurrence
As a result of virus-host coadaptation, SIVagmVer infection is characterized by a lack of disease progression in spite of robust viral replication
Summary
Over 40 African nonhuman primate (NHP) species are naturally infected with simian immunodeficiency viruses (SIVs) [1,2,3]. African green monkeys (AGMs) (Chlorocebus genus) are the most numerous, most widely geographically spread and most commonly infected with SIV in the wild [1]. According to Groves [4,5], AGMs are divided into species that are phenotypically and geographically distinct: vervets (C. pygerythrus) are the most widely spread in East and Southern Africa, ranging from the eastern Rift Valley in Ethiopia, Somalia and extreme southern Sudan to the Cape region in South Africa; grivets (C. aethiops) inhabit the area east of the White Nile in Ethiopia, Somalia from Khartoum to Mongalla, Eritrea and Ethiopia south to the Omo; tantalus monkeys (C. tantalus) are the prevalent species in north Central Africa from Ghana to Sudan and Kenya; green monkeys (C. sabaeus) reside in West Africa from Senegal to the Volta River, and have been introduced to Cape Verde Island as well as to the Caribbean [4]. A fifth AGM species, the malbrouck (C. cynosuros), is located in Central and South-
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