ANRS 12255

Identification et prévalences des SIVs chez les primates non-humains sauvages afin d'estimer les risques de nouvelles transmissions inter-espèces et d'étudier plus en détails les réservoirs des ancêtres du HIV-1 chez les grands singes en Afrique Centrale.

 

Contexte et Objectifs

The main objective of the present application, is the identification and risk assessment of additional SIV transmissions from wild living primate populations to humans and a thorough exploration of the HIV-1 reservoir ancestors in the great apes from west-central Africa (Cameroon, Gabon and DRC). The specific objectives are:
- (1) to determine the prevalence, geographic distribution and the host species  of  the ancestors of the different groups of HIV-1, since this may also yield insight into the circumstances by which chimpanzees, gorillas and/or humans initially acquired SIV or HIV-1 and allows to compare host specific mechanisms of virus adaptation and pathogenicity; 
- (2) to determine the prevalence, geographic distribution of SIV in non-human primates (NHP) which are frequently hunted in order to asses which pathogens may be a risk for humans ;
- (3) to document whether other SIVs crossed the species barrier from primates to humans ; (4) to document to what extent SIV infection has a negative impact on the survival of  wild chimpanzee and gorilla populations.
Durée (en nombre de mois): 
36

 

Avancement

1. Identify the ape reservoir(s) of HIV-1 in west central Africa. In Cameroon, SIVgor infection was identified at a new site, and the new SIVgor viruses are more closely related to HIV-1 group P than any other SIV. It is the first clear evidence that SIVgor has been transmitted to humans and that gorilla populations from southwest Cameroon were the source of HIV-1 group P. In North-east Gabon, fecal samples were collected from wild living chimpanzees at 2 remote forest sites with high SIVcpzPtt prevalences. At least 80 SIVcpz positive chimpanzees (51 males and 29 females) were identified and SIVcpzPtt sequences were obtained from 40 individuals. Phylogenetic analyses specific phylogeographic clade of SIVcpz strains from north-east Gabon. We screened bonobos (Pan paniscus) in the DRC, a species not previously tested for SIV in the wild. In contrast to chimpanzees from DRC which are infected with SIVcpzPtt at high rates,13.4% (95% confidence interval, 10.7% to 16.5%), none of the 650 bonobo samples from 8 sites was antibody positive.
 
2. Determine which non-human primate species in gabon and drc are naturally infected with SIV, evaluate their infection rates in the wild and estimate the risk for cross-species transmissions to humans. In Gabon, we conducted a pilot study on NHP bushmeat seized by the competent authorities in different locations across the country. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described.We also show that within one species, a high genetic diversity may exist for SIVs and STLVs and observe a high genetic diversity in the SIVgsn/mon/mus lineage, ancestor of HIV-1/SIVcpz/SIVgor. In the Democratic Republic of Congo, we collected 330 samples derived from nonhuman primate bushmeat at 3 remote forest sites. 19% of NHP bushmeat was infected with SIVs, and new SIV lineages were identified. Highest SIV prevalences were seen in red-tailed guenons (25%) and Tshuapa red colobus monkeys (24%), representing the most common hunted primate species, thus increasing the likelihood for cross-species transmission. 7.9% of NHP bushmeat is infected with STLVs.
 
3. Determine whether primates continue to serve as a reservoir for human infection. In collaboration with Dr. F.Leendertz from the Robert Koch Institute we tested plasma samples from 774 individuals living in 18 rural villages bordering the Taï National Park, Côte d’Ivoire, for the presence of HIV/SIV cross-reactive antibodies using 24 HIV/SIV lineage specific antigens in an in-house Luminex-based EIA. We identified a novel HIV-2 variant (HIV-2-07IC-TNP03) not related to any of the previously defined HIV-2 groups. The finding of this 9th HIV-2 outbreak shows that our knowledge on HIV diversity is far from being complete. In collaboration with Nathan Wolfe from GVFI (Global Forecasting Initiative), we evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, in a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus.
 
4. Study whether SIV infection in chimpanzees and gorillas is associated with disease. Between 2004 and 2011, 961 gorilla fecal samples were collected at the Campo Ma'an National Park, Cameroon. Among them, 16% cross-reacted with HIV-1 antibodies, corresponding to at least 34 infected gorillas. Combining host genotyping and field data, we identified four social groups composed of 7 to 15 individuals each, with SIV rates ranging from 13% to 29%. Eleven SIVgor-infected gorillas were sampled multiple times; two most likely seroconverted during the study period, showing that SIVgor continues to spread. Phylogenetic analysis of partial env and pol sequences revealed cocirculation of closely related and divergent strains among gorillas from the same social group, indicating SIVgor transmissions within and between groups. Parental links could be inferred for some gorillas infected with closely related strains, suggesting vertical transmission, but horizontal transmission by sexual or aggressive behavior was also suspected. Intrahost molecular evolution in one gorilla over a 5-year period showed viral adaptations characteristic of escape mutants, i.e., V1V2 loop elongation and an increased number of glycosylation sites. Here we show for the first time the feasibility of noninvasive monitoring of nonhabituated gorillas to study SIVgor infection over time at both the individual and population levels. This approach can also be applied more generally to study other pathogens in wildlife.

Perspectives

Our studies will provide better knowledge on:

  1. SIVcpz and SIVgor diversity as well as whether group M and N ancestors are restricted to chimpanzees and group O ancestors to gorillas,
  2. whether group M ancestors are restricted to the extreme south-east of Cameroon or if such variants are also present in ape populations in neighboring regions, especially in Gabon,
  3. whether chimpanzees harboring SIVgor like viruses infected gorillas and humans independently; or whether chimpanzees harboring SIVgor like viruses infect only gorillas, who then passed the virus on to humans,
  4. whether bonobos and mountain gorillas are infected with SIV,
  5. estimate risk for potential new cross-species transmission with SIVs from primate bushmeat
  6. whether SIV cross-species transmissions have actually been missed, and whether new SIVs will be found in the context of HIV-1 group M infections because of the potential for recombination with circulating HIV-1 strains
  7. whether SIV infections have a negative impact on health and survival of great apes.
SFP TIE InfVIH
Situation Actuelle: 
Terminé