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Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

ABSTRACT: Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (n = 2,367) and eastern Grauer gorillas (n = 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpzPtt in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas.

SUBMITTER: Neel C

PROVIDER: S-EPMC2812320 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

Neel Cécile C Etienne Lucie L Li Yingying Y Takehisa Jun J Rudicell Rebecca S RS Bass Innocent Ndong IN Moudindo Joseph J Mebenga Aimé A Esteban Amandine A Van Heuverswyn Fran F Liegeois Florian F Kranzusch Philip J PJ Walsh Peter D PD Sanz Crickette M CM Morgan David B DB Ndjango Jean-Bosco N JB Plantier Jean-Christophe JC Locatelli Sabrina S Gonder Mary K MK Leendertz Fabian H FH Boesch Christophe C Todd Angelique A Delaporte Eric E Mpoudi-Ngole Eitel E Hahn Beatrice H BH Peeters Martine M

Journal of virology 20091111 3

Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiologi ...[more]

PMID: 19906908

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Project description:Western lowland gorillas (Gorilla gorilla gorilla) are infected with a simian immunodeficiency virus (SIVgor) that is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively) in west central Africa. Although existing data suggest a chimpanzee origin for SIVgor, a paucity of available sequences has precluded definitive conclusions. Here, we report the molecular characterization of one partial (BQ664) and three full-length (CP684, CP2135, and CP2139) SIVgor genomes amplified from fecal RNAs of wild-living gorillas at two field sites in Cameroon. Phylogenetic analyses showed that all SIVgor strains clustered together, forming a monophyletic lineage throughout their genomes. Interestingly, the closest relatives of SIVgor were not SIVcpzPtt strains from west central African chimpanzees (Pan troglodytes troglodytes) but human viruses belonging to HIV-1 group O. In trees derived from most genomic regions, SIVgor and HIV-1 group O formed a sister clade to the SIVcpzPtt lineage. However, in a tree derived from 5' pol sequences ( approximately 900 bp), SIVgor and HIV-1 group O fell within the SIVcpzPtt radiation. The latter was due to two SIVcpzPtt strains that contained mosaic pol sequences, pointing to the existence of a divergent SIVcpzPtt lineage that gave rise to SIVgor and HIV-1 group O. Gorillas appear to have acquired this lineage at least 100 to 200 years ago. To examine the biological properties of SIVgor, we synthesized a full-length provirus from fecal consensus sequences. Transfection of the resulting clone (CP2139.287) into 293T cells yielded infectious virus that replicated efficiently in both human and chimpanzee CD4(+) T cells and used CCR5 as the coreceptor for viral entry. Together, these results provide strong evidence that P. t. troglodytes apes were the source of SIVgor. These same apes may also have spawned the group O epidemic; however, the possibility that gorillas served as an intermediary host cannot be excluded.

Project description:Simian immunodeficiency virus of chimpanzees (SIVcpz) is the immediate precursor to human immunodeficiency virus type 1 (HIV-1), yet remarkably, the distribution and prevalence of SIVcpz in wild ape populations are unknown. Studies of SIVcpz infection rates in wild chimpanzees are complicated by the species' endangered status and by its geographic location in remote areas of sub-Saharan Africa. We have developed sensitive and specific urine and fecal tests for SIVcpz antibody and virion RNA (vRNA) detection and describe herein the first comprehensive prevalence study of SIVcpz infection in five wild Pan troglodytes schweinfurthii communities in east Africa. In Kibale National Park in Uganda, 31 (of 52) members of the Kanyawara community and 39 (of approximately 145) members of the Ngogo community were studied; none were found to be positive for SIVcpz infection. In Gombe National Park in Tanzania, 15 (of 20) members of the Mitumba community, 51 (of 55) members of the Kasekela community, and at least 10 (of approximately 20) members of the Kalande community were studied. Seven individuals were SIVcpz antibody and/or vRNA positive, and two others had indeterminate antibody results. Based on assay sensitivities and the numbers and types of specimens analyzed, we estimated the prevalence of SIVcpz infection to be 17% in Mitumba (95% confidence interval, 10 to 40%), 5% in Kasekela (95% confidence interval, 4 to 7%), and 30% in Kalande (95% confidence interval, 15 to 60%). For Gombe as a whole, the SIVcpz prevalence was estimated to be 13% (95% confidence interval, 7 to 25%). SIVcpz infection was confirmed in five chimpanzees by PCR amplification of partial pol and gp41/nef sequences which revealed a diverse group of viruses that formed a monophyletic lineage within the SIVcpzPts radiation. Although none of the 70 Kibale chimpanzees tested SIVcpz positive, we estimated the likelihood that a 10% or higher prevalence existed but went undetected because of sampling and assay limitations; this possibility was ruled out with 95% certainty. These results indicate that SIVcpz is unevenly distributed among P. t. schweinfurthii in east Africa, with foci or "hot spots" of SIVcpz endemicity in some communities and rare or absent infection in others. This situation contrasts with that for smaller monkey species, in which infection rates by related SIVs are generally much higher and more uniform among different groups and populations. The basis for the wide variability in SIVcpz infection rates in east African apes and the important question of SIVcpz prevalence in west central African chimpanzees (Pan troglodytes troglodytes) remain to be elucidated.

Project description:Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) and Ebola virus. Simian foamy viruses (SFVs) are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes) using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724) were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706) or viral nucleic acids (n = 392). SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz); however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp), pol-RT (717 bp), and pol-IN (425 bp) sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey species, indicating cross-species transmission of SFVs in the wild. These data indicate that SFVcpz (i) is widely distributed among all chimpanzee subspecies; (ii) is shed in fecal samples as viral RNA; (iii) is transmitted predominantly by horizontal routes; (iv) is prone to superinfection and recombination; (v) has co-evolved with its natural host; and (vi) represents a sensitive marker of population structure that may be useful for chimpanzee taxonomy and conservation strategies.

Project description:UNLABELLED:Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains. In addition, apex V2-directed bNabs (n = 3) as well as llama-derived (heavy chain only) antibodies (n = 6) recognizing both the CD4 binding site and gp41 epitopes were either completely inactive or neutralized only a fraction of SIVcpzPtt strains. In contrast, one antibody targeting the membrane-proximal external region (MPER) of gp41 (10E8), functional CD4 and CCR5 receptor mimetics (eCD4-Ig, eCD4-Ig(mim2), CD4-218.3-E51, and CD4-218.3-E51-mim2), as well as mono- and bispecific anti-human CD4 (iMab and LM52) and CCR5 (PRO140, PRO140-10E8) receptor antibodies neutralized >90% of SIVcpz and SIVgor strains with low-nanomolar (0.13 to 8.4 nM) potency. Importantly, the latter antibodies blocked virus entry not only in TZM-bl cells but also in Cf2Th cells expressing chimpanzee CD4 and CCR5 and neutralized SIVcpz in chimpanzee CD4(+) T cells, with 50% inhibitory concentrations (IC50s) ranging from 3.6 to 40.5 nM. These findings provide new insight into the protective capacity of anti-HIV-1 bNabs and identify candidates for further development to combat SIVcpz infection. IMPORTANCE:SIVcpz is widespread in wild-living chimpanzees and can cause AIDS-like immunopathology and clinical disease. HIV-1 infection of humans can be controlled by antiretroviral therapy; however, treatment of wild-living African apes with current drug regimens is not feasible. Nonetheless, it may be possible to curb the spread of SIVcpz in select ape communities using vectored immunoprophylaxis and/or therapy. Here, we show that antibodies and antibody-like inhibitors developed to combat HIV-1 infection in humans are capable of neutralizing genetically diverse SIVcpz and SIVgor strains with considerable breadth and potency, including in primary chimpanzee CD4(+) T cells. These reagents provide an important first step toward translating intervention strategies currently developed to treat and prevent AIDS in humans to SIV-infected apes.

Dataset Information

Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

Publications

Molecular epidemiology of simian immunodeficiency virus infection in wild-living gorillas.

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