Dataset Information

New strain of simian immunodeficiency virus identified in wild-born chimpanzees from central Africa.

ABSTRACT: Studies of primate lentiviruses continue to provide information about the evolution of simian immunodeficiency viruses (SIVs) and the origin and emergence of HIV since chimpanzees in west-central Africa (Pan troglodytes troglodytes) were recognized as the reservoir of SIVcpzPtt viruses, which have been related phylogenetically to HIV-1. Using in-house peptide ELISAs to study SIV prevalence, we tested 104 wild-born captive chimpanzees from Gabon and Congo. We identified two new cases of SIVcpz infection in Gabon and characterized a new SIVcpz strain, SIVcpzPtt-Gab4. The complete sequence (9093 bp) was obtained by a PCR-based 'genome walking' approach to generate 17 overlapping fragments. Phylogenetic analyses of separated genes (gag, pol-vif and env-nef) showed that SIVcpzPtt-Gab4 is closely related to SIVcpzPtt-Gab1 and SIVcpzPtt-Gab2. No significant variation in viral load was observed during 3 years of follow-up, but a significantly lower CD4+ T cells count was found in infected than in uninfected chimpanzees (p<0.05). No clinical symptoms of SIV infection were observed in the SIV-positive chimpanzees. Further field studies with non-invasive methods are needed to determine the prevalence, geographic distribution, species association, and natural history of SIVcpz strains in the chimpanzee habitat in Gabon.

SUBMITTER: Souquiere S

PROVIDER: S-EPMC3440395 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New strain of simian immunodeficiency virus identified in wild-born chimpanzees from central Africa.

Souquière Sandrine S Makuwa Maria M Sallé Bettina B Kazanji Mirdad M

PloS one 20120912 9

Studies of primate lentiviruses continue to provide information about the evolution of simian immunodeficiency viruses (SIVs) and the origin and emergence of HIV since chimpanzees in west-central Africa (Pan troglodytes troglodytes) were recognized as the reservoir of SIVcpzPtt viruses, which have been related phylogenetically to HIV-1. Using in-house peptide ELISAs to study SIV prevalence, we tested 104 wild-born captive chimpanzees from Gabon and Congo. We identified two new cases of SIVcpz in ...[more]

PMID: 22984489

Similar Datasets

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:Studies of simian immunodeficiency viruses (SIVs) in their endangered primate hosts are of obvious medical and public health importance, but technically challenging. Although SIV-specific antibodies and nucleic acids have been detected in primate fecal samples, recovery of replication-competent virus from such samples has not been achieved. Here, we report the construction of infectious molecular clones of SIVcpz from fecal viral consensus sequences. Subgenomic fragments comprising a complete provirus were amplified from fecal RNA of three wild-living chimpanzees and sequenced directly. One set of amplicons was concatenated using overlap extension PCR. The resulting clone (TAN1.24) contained intact genes and regulatory regions but was replication defective. It also differed from the fecal consensus sequence by 76 nucleotides. Stepwise elimination of all missense mutations generated several constructs with restored replication potential. The clone that yielded the most infectious virus (TAN1.910) was identical to the consensus sequence in both protein and long terminal repeat sequences. Two additional SIVcpz clones were constructed by direct synthesis of fecal consensus sequences. One of these (TAN3.1) yielded fully infectious virus, while the second one (TAN2.69) required modification at one ambiguous site in the viral pol gene for biological activity. All three reconstructed proviruses produced infectious virions that replicated in human and chimpanzee CD4(+) T cells, were CCR5 tropic, and resembled primary human immunodeficiency virus type 1 isolates in their neutralization phenotype. These results provide the first direct evidence that naturally occurring SIVcpz strains already have many of the biological properties required for persistent infection of humans, including CD4 and CCR5 dependence and neutralization resistance. Moreover, they outline a new strategy for obtaining medically important "SIV isolates" that have thus far eluded investigation. Such isolates are needed to identify viral determinants that contribute to cross-species transmission and host adaptation.

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.

Project description:Chimpanzees in west central Africa (Pan troglodytes troglodytes) are endemically infected with simian immunodeficiency viruses (SIVcpzPtt) that have crossed the species barrier to humans and gorillas on at least five occasions, generating pandemic and nonpandemic forms of human immunodeficiency virus type 1 (HIV-1) as well as gorilla SIV (SIVgor). Chimpanzees in east Africa (Pan troglodytes schweinfurthii) are also infected with SIVcpz; however, their viruses (SIVcpzPts) have never been found in humans. To examine whether this is due to a paucity of natural infections, we used noninvasive methods to screen wild-living eastern chimpanzees in the Democratic Republic of the Congo (DRC), Uganda, and Rwanda. We also screened bonobos (Pan paniscus) in the DRC, a species not previously tested for SIV in the wild. Fecal samples (n = 3,108) were collected at 50 field sites, tested for species and subspecies origin, and screened for SIVcpz antibodies and nucleic acids. Of 2,565 samples from eastern chimpanzees, 323 were antibody positive and 92 contained viral RNA. The antibody-positive samples represented 76 individuals from 19 field sites, all sampled north of the Congo River in an area spanning 250,000 km(2). In this region, SIVcpzPts was common and widespread, with seven field sites exhibiting infection rates of 30% or greater. The overall prevalence of SIVcpzPts infection was 13.4% (95% confidence interval, 10.7% to 16.5%). In contrast, none of the 543 bonobo samples from six sites was antibody positive. All newly identified SIVcpzPts strains clustered in strict accordance to their subspecies origin; however, they exhibited considerable genetic diversity, especially in protein domains known to be under strong host selection pressure. Thus, the absence of SIVcpzPts zoonoses cannot be explained by an insufficient primate reservoir. Instead, greater adaptive hurdles may have prevented the successful colonization of humans by P. t. schweinfurthii viruses.

Project description:BackgroundAn assessment of population size and structure is an important first step in devising conservation and management plans for endangered species. Many threatened animals are elusive, rare and live in habitats that prohibit directly counting individuals. For example, a well-founded estimate of the number of great apes currently living in the wild is lacking. Developing methods to obtain accurate population estimates for these species is a priority for their conservation management. Genotyping non-invasively collected faecal samples is an effective way of evaluating a species' population size without disruption, and can also reveal details concerning population structure.Methodology/principal findingsWe opportunistically collected wild chimpanzee faecal samples for genetic capture-recapture analyses over a four-year period in a 132 km(2) area of Loango National Park, Gabon. Of the 444 samples, 46% yielded sufficient quantities of DNA for genotyping analysis and the consequent identification of 121 individuals. Using genetic capture-recapture, we estimate that 283 chimpanzees (range: 208-316) inhabited the research area between February 2005 and July 2008. Since chimpanzee males are patrilocal and territorial, we genotyped samples from males using variable Y-chromosome microsatellite markers and could infer that seven chimpanzee groups are present in the area. Genetic information, in combination with field data, also suggested the occurrence of repeated cases of intergroup violence and a probable group extinction.Conclusions/significanceThe poor amplification success rate resulted in a limited number of recaptures and hence only moderate precision (38%, measured as the entire width of the 95% confidence interval), but this was still similar to the best results obtained using intensive nest count surveys of apes (40% to 63%). Genetic capture-recapture methods applied to apes can provide a considerable amount of novel information on chimpanzee population size and structure with minimal disturbance to the animals and represent a powerful complement to traditional field-based methods.

Dataset Information

New strain of simian immunodeficiency virus identified in wild-born chimpanzees from central Africa.

Publications

New strain of simian immunodeficiency virus identified in wild-born chimpanzees from central Africa.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets