Genetic Characterization of Simian Foamy Viruses Infecting Humans

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Simian foamy viruses (SFV) are retroviruses that are widespread among nonhuman primates. SFV can be transmitted to humans, giving rise to a persistent infection. Only a few data are available concerning the distribution of SFV in human blood cells. Here we purified blood mononuclear cell subsets from 11 individuals infected with a Gorilla gorilla SFV strain and quantified SFV DNA levels by quantitative PCR. SFV DNA was detected in the majority of the CD8 ؉ , CD4 ؉ T cells were positively correlated with the duration of the infection. Our study shows with a quantitative method that CD8 ؉ , CD4 ؉ , and B lymphocytes are major cellular targets of SFV in the blood of infected humans. IMPORTANCE Investigation of SFV infections in humans is important due to the origin of human immunodeficiency viruses (HIV) and human T cell lymphotropic viruses (HTLV) from cross-species transmission of their simian counterparts to humans. Surprisingly little is known about many aspects of the biology of SFV in infected humans, including quantitative data concerning the cellular targets of SFV in vivo.Here we show that the distribution of SFV DNA among the different leukocyte populations is not homogeneous and that viral load in CD4 ؉ T lymphocytes is correlated with the duration of infection. These new data will help in understanding the biology of retroviral infections in humans and can be useful in the growing field of SFV-based gene therapy.

Section: Discussionmentioning

confidence: 91%

“…Of note, we have also found a premature stop codon in the bet gene of the Pan troglodytes troglodytes strain of SFV (from 3 chimpanzees and 4 humans infected with SFV) resulting in a predicted Bet protein that is shortened by 2% (14). These observations led us to sequence the bet coding sequence from the 11 individuals.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Cellular Tropism of Gorilla Simian Foamy Virus in Blood of Infected Humans

Rua

Betsem

Montange

et al. 2014

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“…Our study also revealed natural polymorphisms in gag and bet between SFV strains originating from different chimpanzee subspecies and polymorphisms in U3 and tas at the interindividual level (31). Based on the complete sequence of five replication-competent strains, we found no evidence of viral adaptation among SFV strains isolated from humans (31).…”

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confidence: 80%

“…The strains belonged to the Ggo-FV or Ptr-FV group according to their pol and/or LTR sequences. In addition, we previously obtained complete SFV sequences (Bad468, Bak74, AG15, and Bad327) from four Cameroonian individuals (31). Buffy coat or DNA samples were available for 51 of the remaining 58 individuals.…”

Section: Resultsmentioning

confidence: 99%

Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa

Richard

Rua

Betsem

et al. 2015

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Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. IMPORTANCESFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to humans. These variants differ greatly in the SU region that corresponds to the part of the Env protein in contact with the environment. These variants may have emerged through recombination between SFV strains infecting different NHP species.

“…However, even in the face of this pronounced cospeciation, SFVs have been shown to repeatedly cross species barriers to other NHPs or even humans (4,5,6,7,8,9). It is currently unknown whether genetic adaptation to the new host occurs, for instance, in genes that are at the forefront of hostpathogen interactions (10,11). Here, host-encoded antiviral restriction factors like APOBEC3 cytidine deaminases and the viral proteins counteracting this restriction, like the lentiviral Vif and the FV Bet proteins, are prominent examples for rapid coevolution and cospeciation (12,13,14,15).…”

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confidence: 99%

Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep

Materniak

Hechler

Löchelt

et al. 2013

bFoamy viruses (FVs) are the least known retroviruses commonly found in primates, cats, horses, and cattle. Although FVs are considered apathogenic, simian and feline FVs have been shown to be associated with some transient health abnormalities in animal models. Currently, data regarding the course of infection with bovine FV (BFV) are not available. In this study, we conducted experimental infections of natural (cattle) and heterologous (sheep) hosts with the BFV 100 isolate and monitored infection patterns in both hosts during the early phase postinoculation as well as after long-term infection. Four calves and six sheep inoculated with BFV 100 showed no signs of pathology but developed persistent infection, as confirmed by virus rescue, consistent detection of BFV-specific antibodies, and presence of viral DNA. In both hosts, antibodies against BFV Gag and Bet appeared early after infection and persisted at high and stable levels while seroreactivity toward Env was consistently detectable only in BFV-infected sheep. Interestingly, the BFV proviral DNA load was highest in lung, spleen, and liver and moderate in leukocytes, while salivary glands contained either low or undetectable DNA loads in calves or sheep, respectively. Additionally, comparison of partial BFV sequences from inoculum and infected animals demonstrated very limited changes after long-term infection in the heterologous host, clearly less than those found in BFV field isolates. The persistence of BFV infection in both hosts suggests full replication competence of the BFV 100 isolate with no requirement of genetic adaptation for productive replication in the authentic and even in a heterologous host.