APOBEC3F Constitutes a Barrier to Successful Cross-Species Transmission of Simian Immunodeficiency Virus SIVsmm to Humans.

Simian immunodeficiency virus infecting sooty mangabeys (SIVsmm) has been transmitted to humans on at least nine occasions, giving rise to human immunodeficiency virus type 2 (HIV-2) groups A to I. SIVsmm isolates replicate in human T cells and seem capable of overcoming major human restriction factors without adaptation. However, only groups A and B are responsible for the HIV-2 epidemic in sub-Saharan Africa, and it is largely unclear whether adaptive changes were associated with spread in humans. To address this, we examined the sensitivity of infectious molecular clones (IMCs) of five HIV-2 strains and representatives of five different SIVsmm lineages to various APOBEC3 proteins. We confirmed that SIVsmm strains replicate in human T cells, albeit with more variable replication fitness and frequently lower efficiency than HIV-2 IMCs. Efficient viral propagation was generally dependent on intact vif genes, highlighting the need for counteraction of APOBEC3 proteins. On average, SIVsmm was more susceptible to inhibition by human APOBEC3D, -F, -G, and -H than HIV-2. For example, human APOBEC3F reduced infectious virus yield of SIVsmm by ∼80% but achieved only ∼40% reduction in the case of HIV-2. Functional and mutational analyses of human- and monkey-derived alleles revealed that an R128T polymorphism in APOBEC3F contributes to species-specific counteraction by HIV-2 and SIVsmm Vifs. In addition, a T84S substitution in SIVsmm Vif increased its ability to counteract human APOBEC3F. Altogether, our results confirm that SIVsmm Vif proteins show intrinsic activity against human APOBEC3 proteins but also demonstrate that epidemic HIV-2 strains evolved an increased ability to counteract this class of restriction factors during human adaptation. IMPORTANCE Viral zoonoses pose a significant threat to human health, and it is important to understand determining factors. SIVs infecting great apes gave rise to HIV-1. In contrast, SIVs infecting African monkey species have not been detected in humans, with one notable exception. SIVsmm from sooty mangabeys has crossed the species barrier to humans on at least nine independent occasions and seems capable of overcoming many innate defense mechanisms without adaptation. Here, we confirmed that SIVsmm Vif proteins show significant activity against human APOBEC3 proteins. Our analyses also revealed, however, that different lineages of SIVsmm are significantly more susceptible to inhibition by various human APOBEC3 proteins than HIV-2 strains. Mutational analyses suggest that an R128T substitution in APOBEC3F and a T84S change in Vif contribute to species-specific counteraction by HIV-2 and SIVsmm. Altogether, our results support that epidemic HIV-2 strains acquired increased activity against human APOBEC3 proteins to clear this restrictive barrier.

Broad diversity of simian immunodeficiency virus infecting Chlorocebus species (African green monkey) and evidence of cross-species infection in Papio anubis (olive baboon) in Kenya.

BACKGROUND: Simian immunodeficiency virus (SIV) naturally infects African non-human primates (NHPs) and poses a threat of transmission to humans through hunting and consumption of monkeys as bushmeat. This study investigated the as of yet unknown molecular diversity of SIV in free-ranging Chlorocebus species (African green monkeys-AGMs) and Papio anubis (olive baboons) within Mombasa, Kisumu and Naivasha urban centres in Kenya. METHODS: We collected blood samples from 124 AGMs and 65 olive baboons in situ, and detected SIV by high-resolution melting analysis and sequencing of PCR products. RESULTS: Simian immunodeficiency virus prevalence was 32% in AGMs and 3% in baboons. High-resolution melting (HRM) analysis demonstrated distinct melt profiles illustrating virus diversity confirmed by phylogenetic analysis. CONCLUSIONS: There is persistent evolutionary diversification of SIVagm strains in its natural host, AGMs and cross-species infection to olive baboons is occurring. Further study is required to establish pathogenesis of the diverse SIVagm variants and baboon immunological responses.

Identification of a Novel Simian Immunodeficiency Virus-Infected African Green Monkey (Chlorocebus tantalus) Confirms that Tantalus Monkeys in Cameroon Are Infected with a Mosaic SIVagm Lineage.

In this study we report on the identification of a simian immunodeficiency virus (SIV) infecting a Chlorocebus tantalus from Cameroon. The isolate, SIVagmTAN-CA1, was molecularly characterized by sequencing partial genome (∼4,000 bp) using the conventional Sanger method and the Oxford Nanopore Technology (ONT). In pol and gp41/nef SIVagmTAN-CA1 clusters with SIVagmSAB infecting Chlorocebus sabaeus from West Africa, whereas in env-gp120 it clusters with SIVagmTAN infecting C. tantalus from Central Africa. This mosaic structure is similar to that of a previously reported isolate infecting another tantalus monkey from Cameroon and confirms that the evolution of SIVagm is complex. Our data show that ONT sequencing gives results comparable with conventional Sanger sequencing on SIV and could help in distinguishing recombination and coinfection.

Markovian switching for near-optimal control of a stochastic SIV epidemic model.

As it is known that environmental perturbation is a key component of epidemic models, and Markov process reveals how the noise affects epidemic systems. The paper introduces Markov chain into a stochastic susceptible-infected-vaccination(SIV) epidemic model composed of vaccination and saturated treatment to analyze the near-optimal control. Based on Pontryagin stochastic maximum principle, the paper gives adequate and all necessary conditions for near-optimal control. Numerical simulations are presented to display the theoretical results and verify the effect of treatment control on epidemic diseases.

Socioecological correlates of clinical signs in two communities of wild chimpanzees (Pan troglodytes) at Gombe National Park, Tanzania.

Disease and other health hazards pose serious threats to the persistence of wild ape populations. The total chimpanzee population at Gombe National Park, Tanzania, has declined from an estimated 120 to 150 individuals in the 1960's to around 100 individuals by the end of 2013, with death associated with observable signs of disease as the leading cause of mortality. In 2004, we began a non-invasive health-monitoring program in the two habituated communities in the park (Kasekela and Mitumba) with the aim of understanding the prevalence of health issues in the population, and identifying the presence and impacts of various pathogens. Here we present prospectively collected data on clinical signs (observable changes in health) in the chimpanzees of the Kasekela (n = 81) and Mitumba (n = 32) communities over an 8-year period (2005-2012). First, we take a population approach and analyze prevalence of clinical signs in five different categories: gastrointestinal system (diarrhea), body condition (estimated weight loss), respiratory system (coughing, sneezing etc.), wounds/lameness, and dermatologic issues by year, month, and community membership. Mean monthly prevalence of each clinical sign per community varied, but typically affected <10% of observed individuals. Secondly, we analyze the presence of clinical signs in these categories as they relate to individual demographic and social factors (age, sex, and dominance rank) and simian immunodeficiency virus (SIVcpz) infection status. Adults have higher odds of being observed with diarrhea, loss of body condition, and wounds or lameness when compared to immatures, while males have a higher probability of being observed with wounds or lameness than females. In contrast, signs of respiratory illness appear not to be related to chimpanzee-specific factors and skin abnormalities are very rare. For a subset of known-rank individuals, dominance rank predicts the probability of wounding/lameness in adult males, but does not predict any adverse clinical signs in adult females. Instead, adult females with SIVcpz infection are more likely to be observed with diarrhea, a finding that warrants further investigation. Comparable data are needed from other sites to determine whether the prevalence of clinical signs we observe are relatively high or low, as well as to more fully understand the factors influencing health of wild apes at both the population and individual level. Am. J. Primatol. 80:e22562, 2018. © 2016 Wiley Periodicals, Inc.

Phyloepidemiological Analysis Reveals that Viral Divergence Led to the Paucity of Simian Immunodeficiency Virus SIVmus/gsn/mon Infections in Wild Populations.

Human immunodeficiency virus type 1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red-capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalences and an uneven geographic distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn, respectively, also have low rates of SIV infections in their populations. Compared to that for other monkeys, including red-capped mangabeys and closely related guenon species, such an epidemiology is unusual. By intensifying sampling of geographically distinct populations of mustached and greater spot-nosed guenons in Gabon and including large sample sets of mona guenons from Cameroon, we add strong support to the hypothesis that the paucity of SIV infections in wild populations is a general feature of this monophyletic group of viruses. Furthermore, comparative phylogenetic analysis reveals that this phenotype is a feature of this group of viruses infecting phylogenetically disparate hosts, suggesting that this epidemiological phenotype results from infection with these HIV-1-related viruses rather than from a common host factor. Thus, these HIV-1-related viruses, i.e., SIVcpz and the guenon viruses which share an ancestor with part of the SIVcpz genome, have an epidemiology distinct from that found for SIVs in other African primate species.IMPORTANCE Stable virus-host relationships are established over multiple generations. The prevalence of viral infections in any given host is determined by various factors. Stable virus-host relationships of viruses that are able to cause persistent infections and exist with high incidences of infection are generally characterized by a lack of morbidity prior to host reproduction. Such is the case for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections of humans. SIV infections of most African primate species also satisfy these criteria, with these infections found at a high prevalence and with rare cases of clinical disease. In contrast, SIVcpz, the ancestor of HIV-1, has a different epidemiology, and it has been reported that infected animals suffer from an AIDS-like disease in the wild. Here we conclusively demonstrate that viruses which are closely related to SIVcpz and infect a subset of guenon monkeys show an epidemiology resembling that of SIVcpz.

Isolation of a simian immunodeficiency virus from a malbrouck (Chlorocebus cynosuros).

To investigate the diversity of simian immunodeficiency virus (SIV) among nonhuman primates (NHPs) in Zambia, next-generation sequencing was performed to determine the complete genome sequence of a novel SIV recovered by co-culturing African green monkey (AGM) peripheral blood lymphocytes with human CD4+ T-cell lines. We report the first described SIV (SIVagmMAL-ZMB) from a malbrouck (Chlorocebus cynosuros). SIVagmMAL-ZMB was detected by real-time PCR analysis of splenic RNA in 3.2% (3/94) of AGMs and was undetectable in baboons (0/105). SIVagmMAL-ZMB possessed <80% nucleotide sequence identity to known SIV isolates and was located basally to vervet monkey SIV strains in all phylogenies.

The Potency of Nef-Mediated SERINC5 Antagonism Correlates with the Prevalence of Primate Lentiviruses in the Wild.

The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors. Additionally, Nefs of HIV and most SIVs rely on the dileucine motif in the C-terminal loop for anti-SERINC5 activity, while the Nef from colobus SIV (SIVcol) evolved different inhibitory mechanisms. We also found a significant correlation between anti-SERINC5 potency and the SIV prevalence in the respective ape and monkey species. Thus, Nef-mediated SERINC5 antagonism may determine the ability of primate lentiviruses to spread within natural hosts.

Why Are Nigeria-Cameroon Chimpanzees (Pan troglodytes ellioti) Free of SIVcpz Infection?

Simian immunodeficiency virus (SIV) naturally infects two subspecies of chimpanzee: Pan troglodytes troglodytes from Central Africa (SIVcpzPtt) and P. t. schweinfurtii from East Africa (SIVcpzPts), but is absent in P. t. verus from West Africa and appears to be absent in P. t. ellioti inhabiting Nigeria and western Cameroon. One explanation for this pattern is that P. t. troglodytes and P. t schweinfurthii may have acquired SIVcpz after their divergence from P. t. verus and P. t. ellioti. However, all of the subspecies, except P. t. verus, still occasionally exchange migrants making the absence of SIVcpz in P. t. ellioti puzzling. Sampling of P. t. ellioti has been minimal to date, particularly along the banks of the Sanaga River, where its range abuts that of P. t. troglodytes. This study had three objectives. First, we extended the sampling of SIVcpz across the range of chimpanzees north of the Sanaga River to address whether under-sampling might account for the absence of evidence for SIVcpz infection in P. t. ellioti. Second, we investigated how environmental variation is associated with the spread and prevalence of SIVcpz in the two chimpanzee subspecies inhabiting Cameroon since environmental variation has been shown to contribute to their divergence from one another. Finally, we compared the prevalence and distribution of SIVcpz with that of Simian Foamy Virus (SFV) to examine the role of ecology and behavior in shaping the distribution of diseases in wild host populations. The dataset includes previously published results on SIVcpz infection and SFVcpz as well as newly collected data, and represents over 1000 chimpanzee fecal samples from 41 locations across Cameroon. Results revealed that none of the 181 P. t. ellioti fecal samples collected across the range of P. t. ellioti tested positive for SIVcpz. In addition, species distribution models suggest that environmental variation contributes to differences in the distribution and prevalence of SIVcpz and SFVcpz. The ecological niches of these two viruses are largely non-overlapping, although stronger statistical support for this conclusion will require more sampling. Overall this study demonstrates that SIVcpz infection is absent or very rare in P. t. ellioti, despite multiple opportunities for transmission. The reasons for its absence remain unclear, but might be explained by one or more factors, including environmental variation, viral competition, and/or local adaptation-all of which should be explored in greater detail through continued surveillance of this region.

HIV-1 Group O Origin, Evolution, Pathogenesis, and Treatment: Unraveling the Complexity of an Outlier 25 Years Later.

Twenty-five years ago, an aberrant HIV-1 (now classified as HIV-1 group O) was described from a Cameroonian HIV patient living in Belgium. The epicenter of group O was later found to be in Central Africa, overlapping with the geographical location of the central chimpanzees (Pan troglodytes troglodytes) and western gorillas (Gorilla gorilla), the likely original hosts of group O. Although the prevalence of group O has remained low at 1-2% in Cameroon, some European countries (France, Spain, Belgium) with strong colonial ties to Central Africa have reported the highest prevalence out of Africa. The sequence diversity between HIV-1 group O and M strains is huge, reaching 50 and 30% in the envelope and pol, respectively. This diversity has hindered diagnosis, monitoring, and treatment of group O-infected patients. Due to the intrinsic presence of the C181 mutation in group O, more than 60% of the approximately 30,000 individuals that live with this virus are faced with the challenge of drug resistance to some currently used antiretroviral therapies, notably the non-nucleoside reverse transcriptase inhibitors. Despite its susceptibility to most antiretroviral therapies, some group Os show a high variable baseline susceptibility to enfuvirtide (T20) and maraviroc. Group O strains are the least fit among all HIV-1 and -2 and restrict tetherin using their Nef but not Vpu as reported for group M. Although limited follow-up studies indicate that the natural course of group O is similar to that of M, these viruses are dominantly CCR5 tropic even late in infection, suggesting slow disease progression. This review summarizes important findings that marked the discovery, origin, spread, evolution, pathogenesis, and treatment of group O within the last 25 years.

High Rate of Simian Immunodeficiency Virus (SIV) Infections in Wild Chimpanzees in Northeastern Gabon.

The emergence of HIV-1 groups M, N, O, and P is the result of four independent cross-species transmissions between chimpanzees (cpz) and gorillas (gor) from central/south Cameroon and humans respectively. Although the first two SIVcpz were identified in wild-born captive chimpanzees in Gabon in 1989, no study has been conducted so far in wild chimpanzees in Gabon. To document the SIVcpz infection rate, genetic diversity, and routes of virus transmission, we analyzed 1458 faecal samples collected in 16 different locations across the country, and we conducted follow-up missions in two of them. We found 380 SIV antibody positive samples in 6 different locations in the north and northeast. We determined the number of individuals collected by microsatellite analysis and obtained an adjusted SIV prevalence of 39.45%. We performed parental analysis to investigate viral spread between and within communities and found that SIVs were epidemiologically linked and were transmitted by both horizontal and vertical routes. We amplified pol and gp41 fragments and obtained 57 new SIVcpzPtt strains from three sites. All strains, but one, clustered together within a specific phylogeographic clade. Given that these SIV positive samples have been collected nearby villages and that humans continue to encroach in ape's territories, the emergence of a new HIV in this area needs to be considered.

Origin of the HIV-1 group O epidemic in western lowland gorillas.

HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples from western lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids. Despite testing wild troops throughout southern Cameroon (n = 14), northern Gabon (n = 16), the Democratic Republic of Congo (n = 2), and Uganda (n = 1), SIVgor was identified at only four sites in southern Cameroon, with prevalences ranging from 0.8-22%. Amplification of partial and full-length SIVgor sequences revealed extensive genetic diversity, but all SIVgor strains were derived from a single lineage within the chimpanzee SIV (SIVcpz) radiation. Two fully sequenced gorilla viruses from southwestern Cameroon were very closely related to, and likely represent the source population of, HIV-1 group P. Most of the genome of a third SIVgor strain, from central Cameroon, was very closely related to HIV-1 group O, again pointing to gorillas as the immediate source. Functional analyses identified the cytidine deaminase APOBEC3G as a barrier for chimpanzee-to-gorilla, but not gorilla-to-human, virus transmission. These data indicate that HIV-1 group O, which spreads epidemically in west central Africa and is estimated to have infected around 100,000 people, originated by cross-species transmission from western lowland gorillas.

Using the pathogenic and nonpathogenic nonhuman primate model for studying non-AIDS comorbidities.

With the advent of antiretroviral therapy that can control virus replication below the detection levels of conventional assays, a new clinical landscape of AIDS emerged, in which non-AIDS complications prevail over AIDS-defining conditions. These comorbidities are diverse and affect multiple organs, thus resulting in cardiovascular, kidney, neurocognitive and liver disease, osteopenia/osteoporosis, and cancers. A common feature of these conditions is that they are generally associated with accelerated aging. The mechanism behind these comorbidities is chronic excessive inflammation induced by HIV infection, which persists under antiretroviral therapy. Progressive simian immunodeficiency virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these comorbidities and offers a simplified system in which most of the traditional human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent. Additionally, experimental conditions can be properly controlled during a shorter course of disease for SIV infection. As such, NHPs can be employed to characterize new paradigms of AIDS pathogenesis and to test the efficacy of interventions aimed at alleviating non-AIDS-related comorbidities.

Quantifying transmission by stage of infection in the field: the example of SIV-1 and STLV-1 infecting mandrills.

The early stage of viral infection is often followed by an important increase of viral load and is generally considered to be the most at risk for pathogen transmission. Most methods quantifying the relative importance of the different stages of infection were developed for studies aimed at measuring HIV transmission in Humans. However, they cannot be transposed to animal populations in which less information is available. Here we propose a general method to quantify the importance of the early and late stages of the infection on micro-organism transmission from field studies. The method is based on a state space dynamical model parameterized using Bayesian inference. It is illustrated by a 28 years dataset in mandrills infected by Simian Immunodeficiency Virus type-1 (SIV-1) and the Simian T-Cell Lymphotropic Virus type-1 (STLV-1). For both viruses we show that transmission is predominant during the early stage of the infection (transmission ratio for SIV-1: 1.16 [0.0009; 18.15] and 9.92 [0.03; 83.8] for STLV-1). However, in terms of basic reproductive number (R0 ), which quantifies the weight of both stages in the spread of the virus, the results suggest that the epidemics of SIV-1 and STLV-1 are mainly driven by late transmissions in this population.

Chronic binge alcohol administration accentuates expression of pro-fibrotic and inflammatory genes in the skeletal muscle of simian immunodeficiency virus-infected macaques.

BACKGROUND: Chronic binge alcohol (CBA) administration exacerbates skeletal muscle (SKM) wasting at the terminal stage of simian immunodeficiency virus (SIV) infection in rhesus macaques. This is associated with a pro-inflammatory and oxidative milieu which we have previously shown to be associated with a disrupted balance between anabolic and catabolic mechanisms. In this study, we attempted to characterize the SKM gene expression signature in CBA-administered SIV-infected macaques, using the same animals from the previous study. METHODS: Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. Gene transcriptomes of SKM excised at necropsy (~10 months post-SIV) from healthy na\xEFve control (Control), sucrose-administered, SIV-infected (SUC-SIV), and CBA-administered, SIV-infected (CBA-SIV) macaques were evaluated in microarray data sets. The Protein Analysis Through Evolutionary Relationships classification tool was used to filter differentially regulated genes based on their predicted function into select biological processes relevant to SKM wasting which were inflammation, extracellular matrix (ECM) remodeling, and metabolism. RESULTS: In total, 1,124 genes were differentially regulated between SUC-SIV and Controls, 2,022 genes were differentially expressed between the CBA-SIV and Controls, and 836 genes were differentially expressed between CBA-SIV and SUC-SIV animals. The relevance of altered gene expression was reflected in the up-regulation of pro-inflammatory CCL-2, CCL-8, CX3CL1, SELE, HP, and TNFRS10A mRNA expression. In addition, ECM remodeling was reflected in the up-regulation of TIMP-1, MMP 2, and MMP 9 mRNA expression and transforming growth factor-beta 1 protein expression. In addition, hydroxyproline content and picrosirius staining reflected increased collagen deposition in the CBA-SIV muscle tissue. CONCLUSIONS: The results of the study demonstrate SKM inflammation as an important underlying mechanism for muscle wasting. In addition, the study provides evidence of SKM fibrotic transformation as a factor in CBA-induced accentuation of SIV-associated muscle wasting.

Assessment of gastrointestinal parasites in wild chimpanzees (Pan troglodytes troglodytes) in southeast Cameroon.

We tested 114 faecal samples from wild simian immunodeficiency virus (SIV)-positive (n = 43) and SIV-negative (n = 71) chimpanzees (Pan troglodytes troglodytes) in southeast Cameroon for the presence of gastrointestinal parasites by direct smear. We observed cysts from different protozoa (Entamoeba coli and Entamoeba histolytica / Entamoeba dispar, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Balantidium coli and Blastocystis cells) and trophozoites from Troglodytella abrassarti and Balantidium coli. Eggs from different helminths (strongylids, Ascaris lumbricoides, Abbreviata caucasica, Trichuris sp., Capillaria sp., Enterobius anthropopeci, Bertiella sp., Hymenolepis diminuta and an undetermined fluke) were also observed. Finally, we observed eggs that could not be properly identified and classified. We did not observe any differences between the SIV+ and SIV- samples except for the unidentified eggs. The studied chimpanzees were highly parasitised by strongylid (85.1% of prevalence), Troglodytella (43.8%) and Blastocystis (2.9%), and the frequency of the other parasites ranged from 0.9 to 8.8%. These high levels of parasite infections could represent an additional burden in a population where there is a high rate of the SIV virus in circulation.

SIVagm infection in wild African green monkeys from South Africa: epidemiology, natural history, and evolutionary considerations.

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.

Natural simian immunodeficiency virus transmission in mandrills: a family affair?

Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.

New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon.

BACKGROUND: Human retroviral infections such as Human Immunodeficiency Virus (HIV) or Human T-cell Lymphotropic Virus (HTLV) are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP) or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV) and Simian T-cell Lymphotropic Viruses (STLV) to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. RESULTS: SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. 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. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus). 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 SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (sub)species can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. CONCLUSIONS: Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to document SIV strains to which humans are exposed. 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.

Pathologic lesions in chimpanzees (Pan trogylodytes schweinfurthii) from Gombe National Park, Tanzania, 2004-2010.

During a population decline or disease outbreak, the true risk of specific diseases to a wild population is often difficult to determine because of a lack of baseline disease information. To better understand the risk of disease in an endangered and scientifically important population of chimpanzees (Pan trogylodytes schweinfurthii), a health monitoring program was initiated in Gombe National Park, Tanzania. As part of this health monitoring program, comprehensive necropsies with histopathology were conducted on chimpanzees (n = 11; 5 male, 6 female), ranging in age from fetal to 44 yr, that were found dead between August 2004 and January 2010. In contrast to previous reports, respiratory disease was not noted as a cause of morbidity or mortality. Trauma was the most common cause of death in these 11 chimpanzees. All of the chimpanzees greater than 1 yr of age had intestinal and mesenteric parasitic granulomas associated with true strongyles consistent with Oesophagostomum spp. The relative numbers of granulomas increased with age and, in some cases, may have been a cause of weight loss and diarrhea. Simian immunodeficiency virus (SIV)cpz infection was documented in four deceased apes, all of whom exhibited varying amounts of lymphoid depletion including two females with marked CD4+ T cell loss consistent with endstage SIVmac or human immunodeficiency virus infections. Myocardial megalokaryosis was common in chimpanzees greater than 1 mo of age; yet myocardial interstitial fibrosis, a common lesion in captive chimpanzees, was uncommon and only noted in two aged chimpanzees. These findings provide important information on causes of morbidity and mortality in wild chimpanzees, information that can be used to interpret findings during population declines and lead to better management of this population in the context of disease risk.