307,745 research outputs found
Simian immunodeficiency virus infection in wild-caught chimpanzees from Cameroon
No full textSimian immunodeficiency viruses (SlVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SlVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SfVcpzCAM5 from Cameroon, indicating the existence of divergent SlVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SlVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study.</p
Simian immunodeficiency virus (SIV) from sun-tailed monkeys (Cercopithecus solatus):Evidence for host-dependent evolution of SIV within the C. lhoesti superspecies
No full textRecently we reported the characterization of simian immunodeficiency virus (SIVlhoest) from a central African l'hoest monkey (Cercopithecus lhoesti lhoesti) that revealed a distant relationship to SIV isolated from a mandrill (SIVmnd). The present report describes a novel SIV (SIVsun) isolated from a healthy, wild-caught sun-tailed monkey (Cercopithecus lhoesti solatus), another member of the l'hoest superspecies. SNsun replicated in a variety of human T-cell lines and in peripheral blood mononuclear cells of macaques (Macaca spp.) and patas monkeys (Erythrocebus patas). A full-length infectious clone of SIVsun was derived, and genetic analysis revealed that SIVsun was most closely related to SIVlhoest, with an amino acid identity of 71% in Gag, 73% in Pol, and 67% in Env. This degree of similarity is reminiscent of that observed between SIVagm isolates from vervet, grivet, and tantalus species of African green monkeys. The close relationship between SNsun and SIVlhoest, despite their geographically distinct habitats, is consistent with evolution from a common ancestor, providing further evidence for the ancient nature of the primate lentivirus family. In addition, this observation leads us to suggest that the SIVmnd lineage should be designated the SIVlhoest lineage.</p
Eastern Chimpanzees, but not Bonobons, represent a simian immunodeficiency virus reservoir
No full textChimpanzees 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 km2. 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
Foci of endemic simian immunodeficiency virus infection in wild-living eastern chimpanzees (Pan troglodytes schweinfurthii)
No full textSimian immunodeficiency virus of chimpanzees (SlVcpz) is the immediate precursor to human immunodeficiency virus type 1 (HIV-1), yet remarkably, the distribution and prevalence of SlVcpz in wild ape populations are unknown. Studies of SlVcpz 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 similar to145) 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 similar to20) 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 pot 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 SlVcpz 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.</p
Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus SIVmac239.
No full textWe examined chemokine receptors for the ability to facilitate the infection of CD4-expressing cells by viruses containing the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. Expression of either human or simian C-C chemokine receptor CCR5 allowed the SIVmac239 envelope glycoproteins to mediate virus entry and cell-to-cell fusion. Thus, distantly related immunodeficiency viruses such as SIV and the primary human immunodeficiency virus type 1 isolates can utilize CCR5 as an entry cofactor
The phylogeography of orangutan foamy viruses supports the theory of ancient repopulation of Sumatra
No full textPhylogenetic analysis of foamy virus sequences obtained from Bornean and Sumatran orangutans showed a distinct clustering pattern. One subcluster was represented by both Bornean and Sumatran orangutan simian foamy viruses (SFV). Combined analysis of host mitochondrial DNA and SFV phylogeny provided evidence for the hypothesis of the repopulation of Sumatra by orangutans from Borneo
Simian immunodeficiency virus (SIV) molecular epidemiology in non-human primates from West Africa
No full textIt is now scientifically proved that the human immunodeficiency viruses, HIV-1
and HIV-2, are the results of cross-species transmissions of the simian
immunodeficiency viruses (SIV) that naturally infect non-human primates in sub-
Saharan Africa. SIVsmm from sooty mangabeys (Cercocebus atys atys) is recognised
as the progenitor of HIV-2, whereas SIVcpz from chimpanzees (Pan troglodytes
troglodytes) and SIVgor from gorillas (Gorilla gorilla gorilla) in West-central Africa are
the ancestors of HIV-1, the virus responsible for the AIDS (Acquired ImmunoDeficiency
Syndrome) pandemic having already infected more than 60 million people.
Only non-human primates (NHPs) species from Africa are infected with SIVs.
Serological evidence of SIV positivity has been shown for at least 40 of the 69 primate
species found in Africa and this has been confirmed by DNA sequence analysis in 32
species.
Generally, SIVs do not induce an AIDS-like syndrome in their natural hosts,
suggesting that they have been associated and evolved with their hosts over an
extended period of time. However, if SIV crosses the species barrier, it may become
pathogenic to the new host. The ancestors of HIV-1 and HIV-2 have crossed the
species barrier to humans on multiple occasions, most likely through the contact with
infected blood and tissues from primates hunted for bushmeat.
Bushmeat hunting has been a longstanding practice throughout sub-Saharan
Africa, but the trade has increased in the last decades. Commercial logging has led to
the construction of roads into remote forest areas and hunters are now making use of
this newly developed infrastructure to penetrate previously inaccessible forests and
capture and transport bushmeat to major city markets. Moreover, villages around
logging concessions have become more densely populated; this has also increased the
trade and consumption around these areas.
The socio-economic and environmental changes occurring combined with the growing
genetic diversity and SIV prevalence among non-human primate populations, suggest
that today, more than previously, the human population is exposed to SIVs. Bushmeat
hunting is not limited to chimpanzees, gorillas or sooty mangabeys: the majority of
NHPs is represented by many Cercopithecus and Colobus species for example. It is
therefore important to continue the search and the characterisation of new SIVs and to
determine the prevalence of infection in the NHP, in order to better evaluate which of
these SIVs represent a health threat for the human population.
The main goal of this thesis were
(i) to determine SIV infection and investigate its prevalence among
different social groups of monkeys living in Taï National Park,
Côte d’Ivoire, knowing that these NHPs are heavily hunted
around this area
(ii) to determine SIV infection and prevalence and to characterise at
a molecular level the SIV possibly infecting the red colobus
species found in Abuko Nature Reserve, the Gambia. Two
different subspecies of red colobus are found in the Gambia and
in Côte d’Ivoire: this represented an opportunity to investigate
whether different subspecies may harbour genetically different
viruses and therefore to better understand the impact of
geographical barriers on the evolution of SIV
(iii) to compare the molecular structure of SIVs infecting red and olive
colobus, two sister species in the Colobinae subfamily
(iv) to determine if the chimpanzee subspecies found in West Africa
is infected with a virus similar to that of the monkey species it
preys upon, knowing that, to date, only the subspecies from
West-central and East Africa have been found to be infected with
SIV.
The majority of the results presented in this thesis have been obtained by
analysing data collected with non-invasive methods. SIV infection has been determined
in NHPs by detecting antibodies or by isolating viral sequences from freshly dropped
faecal samples collected in the forests of Côte d’Ivoire and The Gambia. In order to be
able to discriminate the faecal samples collected and, consequently, to reliably
determine the prevalence of infection in a monkey group, the host has been genotyped
by analysing the DNA extracted from the epithelial cells debris released from the
intestine. Host genotyping, antibody detection and isolation of viral RNA from faecal
samples have become possible thanks to the improvement of conservation methods
and DNA and RNA extraction techniques.
Wild-living non-human primate populations often live in inaccessible areas and
tend to be wary of the presence of observers or display cryptic behaviour; the difficulty in
sampling increases when the target species are arboreal primates exploiting the higher
layers of the forest canopy. To mitigate these problems, we selected two field sites
(Abuko Nature Reserve, The Gambia and Taï National Park, Côte d’Ivoire) where the
primate populations were at least partly habituated by the presence of human observers
and where behavioural-ecology studies have been conducted for more than 10 years.
In fact, SIV is transmitted mainly sexually, but possibly also vertically (from the
mother to the offspring) and through biting or infection of open wounds. It is therefore
important to consider factors such as mating system, patterns of dispersal, group size,
average number of adult males in a group, polyspecific associations, etc. as parameters
conducive to the transmission of the virus within or across groups and species.
In total, more than 300 faecal samples from two groups of western red colobus
(Piliocolobus badius badius), from two groups of black-and-white colobus (Colobus
polykomos polykomos), from three groups of olive colobus (Procolobus verus), from
three groups of Diana monkeys (Cercopithecus diana), from one group of Campbell’s
monkeys (Cercopithecus campbelli), from one group of lesser-spot nosed monkeys
(Cercopithecus petaurista) and from a group of greater spot-nosed monkeys
(Cercopithecus nictitans) were collected near the western border of the Taï Forest, in
Côte d’Ivoire, between March and July 2004.
To discriminate the faecal samples collected, 16 microsatellite loci were screened
in these seven monkey species using cross-specific human markers. Microsatellites are
di-tri-tetra-nucleotide tandem repeats, which length’s variability is transmitted by
Mendelian inheritance and can therefore be used in combination for individual
discrimination. Between 25% to 37% of the primers used were informative and
successfully and reliably amplified faecal extracted DNA from all species (Chapter 5).
Colobus and Cercopithecus samples were first tested for the presence of HIV
cross-reactive antibodies using an immunoblotting assay and were found to be all
negative or ‘non interpretable’.
Subsequently, Reverse Transcriptase-Polymerase Chain Reactions (RT-PCRs) using
universal as well as species-specific primers that target the gag, pol and env regions of
the SIV genome were performed: only the western red colobus tested positive for SIV
infection.
Among the inferred 53 adult individuals belonging to two neighbouring habituated
groups, 14 tested SIVwrc (western red colobus) positive with a prevalence of 26%.
Phylogenetic analysis of pol and env sequences revealed a low degree of viral genetic
diversity in each group. The viral sequences obtained were generally clustering together
according to their respective social group of origin. Conversely, the degree of viral
genetic diversity between the two groups was higher.
Behavioural and demographic data collected previously from these communities
indicate that western red colobus monkeys live in promiscuous multi-male societies,
where females leave their natal group as sub-adults and where extra-group copulations
or male immigration have been rarely observed. Phylogenetic data reflect these
behavioural characteristics (Chapter 6).
The negative SIV results obtained for the other investigated species may reflect
their social structure and mating system, but possibly also the difficulty of group
monitoring, faecal sample collection coverage in the field as well as the long term
conservation of viral RNA in the field and the sensitivity and specificity of SIV serological
and molecular detection tools respectively (Chapter 9).
In parallel, sixteen faecal samples from sixteen individuals and two tissue
samples from two carcasses of Temminck’s red colobus monkeys (Piliocolobus badius
temminckii) collected from the forest floor, between January and February 2005, in the
Abuko Nature Reserve were analysed. None of the 16 faecal samples from Temminck’s
red colobus analysed by RT-PCR were positive. However, SIV infection was identified in
one of the tissue samples, and phylogenetic analyses of partial pol and env sequences
showed that this SIVwrc-Pbt virus strain is closely related to SIVwrc-Pbb strains from
P.b.badius in the Taï Forest, suggesting that geographically separated subspecies can
be infected by closely related viruses. Molecular characterization and phylogenetic
analysis of a SIVwrc-Pbt and two SIVwrc-Pbb full-length genomes, subsequently
sequenced (Chapter 8), confirmed that SIVwrc-Pbt and SIVwrc-Pbb belong to a
species-specific SIV lineage, although distantly related to the SIVlho lineage comprising
SIVs from mandrills (Mandrillus sphinx), l’Hoest (Cercopithecus lhoesti) and sun-tailed
monkeys (Cercopithecus solatus) (Chapters 7 and 8).
More recently, we characterised the full-length genome of the SIV infecting the
olive colobus (SIVolc), by analysing a blood sample collected during a previous study
also conducted in Taï National Park. Olive and western red colobus are sister taxon and
results showed that SIVwrc and SIVolc form distinct lineages, but are closely related
across their entire genome (Chapter 8).
These results confirmed the complex evolutionary history of primate lentiviruses,
which has been driven by host-virus co-speciation, cross-species transmission and
recombination events over an extended period of time. Genomic characterization of
additional SIVs viruses from other Colobines is needed to better understand the
ancestral phylogenetic relationship to SIVs from the l’Hoest lineage and whether
recombination occurred between ancestors of these viruses.
Finally, 5 blood and tissue samples collected from 5 chimpanzee carcasses
during a previous study conducted in Taï National Park, were analysed for SIV infection
in this study. To date, no SIV has been isolated from this subspecies of chimpanzee
(Pan troglodytes verus) found in West Africa. It is known that the chimpanzee hunts
small monkeys and that SIVcpz, the precursor of HIV-1, isolated from the west-central
chimpanzee subspecies (Pan troglodytes troglodytes), is a mosaic virus resulting from
the recombination of viruses from different species of monkeys the chimpanzee preys
upon. Following this line of reasoning, we tested universal as well as species-specific
markers amplifying SIV infecting western red colobus, the favourite prey of chimpanzees
from the Taï Forest. Serological tests conducted on these 5 samples showed a weak
seropositivity in three of them. These results could not be confirmed by PCR. Whether
this chimpanzee subspecies is not infected with SIV or whether it harbours a highly
divergent virus not detected yet by the current molecular tools available remains to be
determined (Chapter 10)
Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection
No full textPersistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al
Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.
No full textSterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed
Human Infections with Plasmodium knowlesi, the Philippines.
No full textFive human cases of infection with the simian malaria parasite Plasmodium knowlesi from Palawan, the Philippines, were confirmed by nested PCR. This study suggests that this zoonotic infection is found across a relatively wide area in Palawan and documents autochthonous cases in the country
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