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Ayalew Mergia - One of the best experts on this subject based on the ideXlab platform.
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preparation of Simian Foamy Virus type 1 vectors
CSH Protocols, 2011Co-Authors: Jeonghae Park, Ayalew MergiaAbstract:Foamy Viruses (FVs) are nonpathogenic retroViruses that offer opportunities for efficient and safe gene transfer in various cell types from different species. These Viruses have unique replication mechanisms that are distinct from other retroViruses, which may give an advantage to FV-mediated gene transfer. This protocol describes a method for Simian Foamy Virus type-1 (SFV-1) vector preparation and concentration. A transient transfection of vector and packaging constructs allows generation of the SFV-1 vector with titers of 10(7)/mL. The vectors can be further concentrated by 100-200-fold without significant loss of vector titer.
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inhibition of Simian immunodeficiency Virus by Foamy Virus vectors expressing sirnas
Virology, 2005Co-Authors: Jeonghae Park, Calvin M Johnson, James R Zucali, Peter E Nadeau, Ayalew MergiaAbstract:Viral vectors available for gene therapy are either inefficient or suffer from safety concerns for human applications. Foamy Viruses are non-pathogenic retroViruses that offer several unique opportunities for gene transfer in various cell types from different species. In this report, we describe the use of Simian Foamy Virus type 1 (SFV-1) vector to examine the efficacy of therapeutic genes. Hairpin short-interfering RNA (siRNA) that targets the Simian immunodeficiency Virus (SIV) rev/env was placed under the control of the PolIII U6 snRNA promoter for expression and screened for silencing target genes using cognate target-reporter fusions. We have identified an effective siRNA (designated R2) which reduces the rev and env gene expression by 89% and 95%, respectively. Using the Simian Foamy Virus type 1 (SFV-1) based vector, we delivered the PolIII expressed R2 siRNA into cultured cells and challenged with SIV. The results show that the R2 siRNA is a potent inhibitor of SIV replication as determined by p27 expression and reverse transcriptase assays. Vectors based on a non-pathogenic SFV-1 vector may provide a safe and efficient alternative to currently available vectors, and the SIV model will help devise protocols for effective anti-HIV gene therapy.
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a minimal genome Simian Foamy Virus type 1 vector system with efficient gene transfer
Virology, 2002Co-Authors: Jeonghae Park, Peter E Nadeau, Ayalew MergiaAbstract:Abstract Foamy Viruses have several inherent features for the opportunity to develop efficient and versatile vectors for gene therapy. We have constructed a series of vectors and helper plasmids based on Simian Foamy Virus type 1 (SFV-1) to establish the minimum vector genome required for efficient gene transduction. To characterize the efficiency of gene transduction by these vectors, the green fluorescent protein (GFP) coding sequence is linked to the human cytomegaloVirus immediate gene promoter. Several deletion analyses of SFV-1 vectors revealed that the minimum genome with efficient GFP transduction contained the 5′ untranslated region extending to the first 637 nucleotides of the gag gene, a 596 nucleotides of pol sequence from position 3137–3733, the 3′ pol region at position 5200–5693, the 3′ end polypurine tract, and the 3′ LTR. An additional 1131 nucleotides can be removed from the 3′ end LTR without affecting the efficiency of vector transduction. SFV-1 vector can therefore accommodate a minimum 8930 base-size heterologous DNA fragment. Furthermore, the efficiency of SFV-1 vector transduction was analyzed using different packaging plasmids. GFP transduction with packaging plasmid that contained the 5′ R-U5 region of the LTR was compared with helper plasmids that had deletions in this region except for 22 nucleotides (positions 21–41), the first 61, 77, or 140 nucleotides of the R of the LTR. Transduction efficiencies were significantly reduced with the deletion mutations implicating that for optimum SFV-1 vector productions a packaging construct that includes the 5′ R-U5 is required.
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transduction of umbilical cord blood cd34 nod scid repopulating cells by Simian Foamy Virus type 1 sfv 1 vector
Virology, 2002Co-Authors: James R Zucali, Jeonghae Park, Calvin M Johnson, Tina Ciccarone, Vicky Kelley, Ayalew MergiaAbstract:Abstract Foamy Viruses are nonpathogenic retroViruses that offer unique opportunities for gene transfer into various cell types including hematopoietic stem cells. We used a Simian Foamy Virus type 1 vector (SFV-1) containing a LacZ reporter gene with a titer of 1–5 × 10 6 viral particles/ml that was free of replication-competent retroVirus to transduce human umbilical cord blood CD34+ cells. Transduced CD34+ cord blood cells were transplanted into NOD/SCID mice and plated in serum-free methylcellulose culture to determine the transduction efficiency of human hematopoietic progenitor cells. A transduction efficiency of about 20% was obtained. At 6–10 weeks posttransplantation, human hematopoietic cell engraftment and marking were determined. Marrow from transplanted mice demonstrated human cell engraftment by the presence of human (CD45+) cells containing both CD19+ lymphoid and CD33+ myeloid cells. Serial sampling of NOD/SCID bone marrow revealed the presence of 6.7–14.0% CD45+ cells at 6 weeks posttransplant as compared to 3.6–27.2% CD45+ cells at 9–10 weeks posttransplant. Human progenitors examined from NOD/SCID bone marrow cells 9 weeks posttransplant revealed from 7.4 to 25.9% of the colonies exhibiting X-gal staining. Our study demonstrates the ability of a Simian Foamy Virus vector to transduce the SCID-repopulating cell and offers a promising new gene delivery system for use in hematopoietic stem cell gene therapy.
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the efficiency of Simian Foamy Virus vector type 1 sfv 1 in nondividing cells and in human pbls
Virology, 2001Co-Authors: Ayalew Mergia, Soumya Chari, Dennis L Kolson, Maureen M Goodenow, Tina CiccaroneAbstract:Current retroviral vectors based on murine leukemia Virus (MuLV) are unable to efficiently transduce nondividing cells. LentiViruses, such as the human immunodeficiency Virus 1 (HIV-1) are efficient at transducing nondividing, growth-arrested, and post-mitotic cells, but due to complex safety considerations, they may have limited potential for human clinical gene transfer. For this reason, alternatives to MuLV and HIV-1 vectors need to be explored. In this paper, we have found that Simian Foamy Virus vector (SFV-1) containing a CMV-LacZ expression cassette is able to efficiently transduce multiple cell types of various species that include epithelial, lymphoid, and hematopoietic-derived human cell lines and fibroblast cell lines of several species. Previously it was reported that Foamy Virus replication is cell cycle dependent (P. D. Bieniasz, R. A. Weiss, and M. O. McClure, 1995. J. Virol. 69, 7295-7299). However, others studies demonstrated nuclear import of viral DNA in arrested cells (A. Saibi, F. Puvion-Dutilleul, M. Schmid, J. Peries, and H. d. The 1997. J. Virol. 71, 1155-1161). Here, we show efficient LacZ transduction by SFV-1 vectors in several chemically arrested cell lines and terminally differentiated human neurons. SFV-1 vector can transduce cell lines arrested in G1/S phase of the cell cycle by aphidicolin treatment with similar efficiencies to that of dividing cells. The terminally differentiated human neural cell line, NT2N, was transduced with 30-50% efficiency, corroborating our data obtained with the arrested cell lines. To further examine whether the SFV-1 vector can efficiently deliver a gene into clinically important cells for gene therapy, we transduced primary human peripheral blood cells (PBLs) in the presence and absence of phytohemagglutanin (PHA) stimulation. We observed 81% transduction efficiency in non-stimulated PBLs and 87% in PHA-stimulated PBLs with vector infection carried out twice in 8 hours intervals at a multiplicity of infection of 1. Together, these data indicate that SFV-1 based retroviral vectors may provide a safe, efficient alternative to current onco- and lentiviral vectors for gene transfer in cells from a broad spectrum of lineages across species boundaries.
Antoine Gessain - One of the best experts on this subject based on the ideXlab platform.
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Modular nature of Simian Foamy Virus genomes and their evolutionary history
Virus Evolution, 2019Co-Authors: Pakorn Aiewsakun, Antoine Gessain, Augustin Mouinga-ondémé, Lea Richard, Philippe Vicente Afonso, Aris KatzourakisAbstract:Among all known retroViruses, Foamy Viruses (FVs) have the most stable Virus–host co-speciation history, co-diverging in concert with their vertebrate hosts for hundreds of millions of years. However, detailed molecular analyses indicate that different parts of their genome might have different evolutionary histories. While their polymerase gene displays a robust and straightforward Virus–host co-speciation pattern, the evolutionary history of their envelope (env) gene, is much more complicated. Here, we report eleven new FV env sequences in two mandrill populations in Central Africa, geographically separated by the Ogooué River into the North and the South populations. Phylogenetic reconstruction of the polymerase gene shows that the two Virus populations are distinct, and each contains two variants of env genes co-existing with one another. The distinction between the two env variants can be mapped to the surface domain, flanked by two recombination hotspots, as previously reported for chimpanzee and gorilla FVs. Our analyses suggest that the two env variants originated during the diversification of Old World monkeys and apes, ∼30 million years ago. We also show that this env gene region forms two phylogenetically distinct clades, each displaying a host co-divergence and geographical separation pattern, while the rest of the genome of the two strains is phylogenetically indistinguishable in each of the host-specific groups. We propose possible evolutionary mechanisms to explain the modular nature of the FV genome.
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modular nature of Simian Foamy Virus genomes and their evolutionary history
Virus Evolution, 2019Co-Authors: Pakorn Aiewsakun, Augustin Mouingaondeme, Antoine Gessain, Lea Richard, Philippe V. Afonso, Aris KatzourakisAbstract:Among all known retroViruses, Foamy Viruses (FVs) have the most stable Virus-host co-speciation history, co-diverging in concert with their vertebrate hosts for hundreds of millions of years. However, detailed molecular analyses indicate that different parts of their genome might have different evolutionary histories. While their polymerase gene displays a robust and straightforward Virus-host co-speciation pattern, the evolutionary history of their envelope (env) gene, is much more complicated. Here, we report eleven new FV env sequences in two mandrill populations in Central Africa, geographically separated by the Ogooue River into the North and the South populations. Phylogenetic reconstruction of the polymerase gene shows that the two Virus populations are distinct, and each contains two variants of env genes co-existing with one another. The distinction between the two env variants can be mapped to the surface domain, flanked by two recombination hotspots, as previously reported for chimpanzee and gorilla FVs. Our analyses suggest that the two env variants originated during the diversification of Old World monkeys and apes, ∼30 million years ago. We also show that this env gene region forms two phylogenetically distinct clades, each displaying a host co-divergence and geographical separation pattern, while the rest of the genome of the two strains is phylogenetically indistinguishable in each of the host-specific groups. We propose possible evolutionary mechanisms to explain the modular nature of the FV genome.
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Clinical Signs and Blood Test Results Among Humans Infected With Zoonotic Simian Foamy Virus: A Case-Control Study
Journal of Infectious Diseases, 2018Co-Authors: Chanceline Ndongo, Edouard Betsem, Richard Njouom, Florence Buseyne, Thomas Montange, Chanceline Bilounga Ndongo, Olivier Hermine, Antoine GessainAbstract:Background. A spillover of Simian Foamy Virus (SFV) to humans, following bites from infected nonhuman primates (NHPs), is ongoing in exposed populations. These retroViruses establish persistent infections of unknown physiological consequences to the human host. Methods. We performed a case-control study to compare 24 Cameroonian hunters infected with gorilla SFV and 24 controls matched for age and ethnicity. A complete physical examination and blood test were performed for all participants. Logistic regression and Wilcoxon signed rank tests were used to compare cases and controls. Results. The cases had significantly lower levels of hemoglobin than the controls (median, 12.7 vs 14.4 g/dL; P = .01). Basophil levels were also significantly lower in cases than controls, with no differences for other leukocyte subsets. Cases had significantly higher urea, creatinine, protein, creatinine phosphokinase, and lactate dehydrogenase levels and lower bilirubin levels than controls. Cases and controls had similar frequencies of general, cutaneous, gastrointestinal, neurological, and cardiorespiratory signs. Conclusions. The first case-control study of apparently healthy SFV-infected Cameroonian hunters showed the presence of hematological abnormalities. A thorough clinical and laboratory workup is now needed to establish the medical relevance of these observations because more than half of cases had mild or moderate anemia. Clinical Trials Registration. NCT03225794.
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Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa
Journal of Virology, 2015Co-Authors: Lea Richard, Edouard Betsem, Augustin Mouinga-ondémé, Richard Njouom, Mirdad Kazanji, Florence Buseyne, Rejane Rua, Éric Leroy, Philippe V. Afonso, Antoine GessainAbstract: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 se-quenced 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. IMPORTANCE SFV 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 recombi-nation between SFV strains infecting different NHP species.
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in vivo cellular tropism of gorilla Simian Foamy Virus in blood of infected humans
Journal of Virology, 2014Co-Authors: Edouard Betsem, Florence Buseyne, Thomas Montange, Rejane Rua, Antoine GessainAbstract: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+, and CD19+ lymphocyte samples and rarely in CD14+ monocyte and CD56+ NK lymphocyte samples. The median (interquartile range [IQR]) SFV DNA counts were 16.0 (11.0 to 49.8), 11.3 (5.9 to 28.3), and 17.2 (2.0 to 25.2) copies/105 cells in CD8+ T lymphocytes, CD4+ T lymphocytes, and CD19+ B lymphocytes, respectively. In the CD4 compartment, SFV DNA was detected in both memory and naive CD4+ T lymphocytes. SFV DNA levels in 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.
Arifa S. Khan - One of the best experts on this subject based on the ideXlab platform.
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complete genome sequence of the african green monkey Simian Foamy Virus serotype 3 strain fv2014 sfvcae_fv2014
Genome Announcements, 2018Co-Authors: Subhiksha Nandakumar, Eunhae H Bae, Arifa S. KhanAbstract:ABSTRACT The full-length sequence of Simian Foamy Virus serotype 3 (SFV-3) strain FV2014, an African green monkey (Chlorocebus aethiops) isolate, was obtained using high-throughput sequencing. SFVcae_FV2014 consisted of 13,127 bp and had a genomic organization similar to those of other SFVs but was distinct from SFV strain LK3, isolated from the same monkey species.
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complete genome sequence of a naturally occurring Simian Foamy Virus isolate from rhesus macaque sfvmmu_k3t
Genome Announcements, 2017Co-Authors: Subhiksha Nandakumar, Eunhae H Bae, Arifa S. KhanAbstract:The full-length genome sequence of a Simian Foamy Virus (SFVmmu_K3T), isolated from a rhesus macaque (Macaca mulatta), was obtained using high-throughput sequencing. SFVmmu_K3T consisted of 12,983 bp and had a genomic organization similar to that of other SFVs, with long terminal repeats (LTRs) and open reading frames for Gag, Pol, Env, Tas, and Bet.
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Identification of Recombination in the Envelope Gene of Simian Foamy Virus Serotype 2 Isolated from Macaca cyclopis
2016Co-Authors: Teresa A. Galvin, Imran A. Ahmed, Muhammad Shahabuddin, Theodore Bryan, Arifa S. KhanAbstract:The full-length sequence of Simian Foamy Virus serotype 2 (SFVmcy-2), isolated from a Taiwanese macaque, was determined. SFVmcy-2 was highly related to SFV serotype 1 (SFVmcy-1), an isolate from the same species, except in the putative receptor binding domain (RBD) in env, which contained novel sequences related to SFV serotype 3 (SFVagm-3), isolated from an African greenmonkey. The results identify a potential region of neutralization in SFVs and demonstrate recombination between geneti-cally divergent Foamy Viruses. Simian Foamy Viruses (SFVs) belong in the SpumaVirus genus ofthe Spumaretrovirinae subfamily of Retroviridae and are wide-spread in all nonhuman primates (NHPs) (1, 2). SFVs have been isolated from various tissues of different NHPs and were originally designated based upon neutralization serotyping (3). Original Foamy Virus isolates were designated SFV serotype 1, SFV serotype 2, and SFV serotype 3 (SFV-1, SFV-2, and SFV-3, respectively). These original monkey isolates were renamed to indicate the spe-cies of isolation (4): SFV-1, which was isolated from a Taiwanese macaque (Formosan Rock macaque or Macaca cyclopis [mcy]) (5, 6), was designated SFVmac, and SFV-3, which was isolated fro
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identification of recombination in the envelope gene of Simian Foamy Virus serotype 2 isolated from macaca cyclopis
Journal of Virology, 2013Co-Authors: Teresa A. Galvin, Imran A. Ahmed, Muhammad Shahabuddin, Theodore Bryan, Arifa S. KhanAbstract:The full-length sequence of Simian Foamy Virus serotype 2 (SFVmcy-2), isolated from a Taiwanese macaque, was determined. SFVmcy-2 was highly related to SFV serotype 1 (SFVmcy-1), an isolate from the same species, except in the putative receptor binding domain (RBD) in env, which contained novel sequences related to SFV serotype 3 (SFVagm-3), isolated from an African green monkey. The results identify a potential region of neutralization in SFVs and demonstrate recombination between genetically divergent Foamy Viruses.
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Role of neutralizing antibodies in controlling Simian Foamy Virus transmission and infection.
Transfusion, 2009Co-Authors: Dhanya K. Williams, Arifa S. KhanAbstract:BACKGROUND: Human infections with Simian Foamy Viruses (SFVs) have been reported after occupational and nonoccupational exposure to infected animals and their tissues, blood, and body fluids, although there is no evidence for human-to-human transmission. We previously demonstrated SFV transmission in monkeys by blood transfusion with whole blood from one donor animal that had a low neutralizing antibody (NAb) endpoint titer, whereas blood transfusion from a second donor monkey that had a high NAb titer failed to transmit Virus. These results suggested a role for NAbs in SFV transmission and establishment of infection. STUDY DESIGN AND METHODS: Whole blood and antibody-reduced blood were transfused into SFV-negative rhesus macaques. SFV infection in recipient animals was monitored by detection of Virus sequences using polymerase chain reaction assays with nucleotide sequence confirmation, by analysis for antibody development in Western blots, and by Virus isolation in coculture assays. NAb titer was evaluated by endpoint dilution assays. RESULTS: SFV transmission by whole blood transfusion from a donor monkey with high NAb endpoint titer failed to establish infection in SFV-negative monkeys, whereas Virus transmission was successful with transfer of antibody-reduced blood cells. CONCLUSIONS: Passive transfer of high-titer NAbs blocked SFV cell–associated transmission, indicating that NAbs may play a role in Virus transmission to individuals exposed to SFV-infected blood and tissues.
Edouard Betsem - One of the best experts on this subject based on the ideXlab platform.
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Clinical Signs and Blood Test Results Among Humans Infected With Zoonotic Simian Foamy Virus: A Case-Control Study
Journal of Infectious Diseases, 2018Co-Authors: Chanceline Ndongo, Edouard Betsem, Richard Njouom, Florence Buseyne, Thomas Montange, Chanceline Bilounga Ndongo, Olivier Hermine, Antoine GessainAbstract:Background. A spillover of Simian Foamy Virus (SFV) to humans, following bites from infected nonhuman primates (NHPs), is ongoing in exposed populations. These retroViruses establish persistent infections of unknown physiological consequences to the human host. Methods. We performed a case-control study to compare 24 Cameroonian hunters infected with gorilla SFV and 24 controls matched for age and ethnicity. A complete physical examination and blood test were performed for all participants. Logistic regression and Wilcoxon signed rank tests were used to compare cases and controls. Results. The cases had significantly lower levels of hemoglobin than the controls (median, 12.7 vs 14.4 g/dL; P = .01). Basophil levels were also significantly lower in cases than controls, with no differences for other leukocyte subsets. Cases had significantly higher urea, creatinine, protein, creatinine phosphokinase, and lactate dehydrogenase levels and lower bilirubin levels than controls. Cases and controls had similar frequencies of general, cutaneous, gastrointestinal, neurological, and cardiorespiratory signs. Conclusions. The first case-control study of apparently healthy SFV-infected Cameroonian hunters showed the presence of hematological abnormalities. A thorough clinical and laboratory workup is now needed to establish the medical relevance of these observations because more than half of cases had mild or moderate anemia. Clinical Trials Registration. NCT03225794.
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Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa
Journal of Virology, 2015Co-Authors: Lea Richard, Edouard Betsem, Augustin Mouinga-ondémé, Richard Njouom, Mirdad Kazanji, Florence Buseyne, Rejane Rua, Éric Leroy, Philippe V. Afonso, Antoine GessainAbstract: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 se-quenced 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. IMPORTANCE SFV 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 recombi-nation between SFV strains infecting different NHP species.
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co circulation of two envelope variants for both gorilla and chimpanzee Simian Foamy Virus strains among humans and apes living in central africa
Retrovirology, 2015Co-Authors: Lea Richard, Edouard Betsem, Rejane Rua, Augustin MouingaondemeAbstract:Simian Foamy Virus (SFV) is a retroVirus ubiquitous in non-human primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory identified more than 50 hunters from Central Africa infected with zoonotic SFVs. Analysis of SFV complete sequences obtained from 5 of these individuals had revealed that the env gene was the most variable one. Furthermore, recombinant SFV strains have been recently shown; some of them involved the env gene. This led us to investigate the env gene variability of zoonotic SFV strains, looking especially for possible recombinants. We sequenced the complete or the surface glycoprotein region (SU) of SFV env gene amplified from blood DNA of: 1) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee FV strain; 2) one gorilla and 3 infected chimpanzees living in the same areas than the hunters. All sequences were aligned and analysed by phylogenetic (neighbour-joining and maximum likelihood) and recombinant detection methods (similarity plot and bootscan analysis, Recombination Detection Program). Phylogenetic analyses revealed the existence of two different env variants among both gorilla FV and chimpanzee FV strains. These were present in zoonotic as well as in NHP strains. These variants differ greatly (more than 30% variability) in a 750 bp long region located in the receptor binding domain of the SU; the rest of the gene is very conserved (less than 5% variability among strains from the same species). Within a given variant, protein sequences of the SU are very conserved and stable (non-synonymous/synonymous mutations ratio <0,1) which may reflect functional constraint. Recombination analyses highlighted that these variants could have emerged through recombination events.
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in vivo cellular tropism of gorilla Simian Foamy Virus in blood of infected humans
Journal of Virology, 2014Co-Authors: Edouard Betsem, Florence Buseyne, Thomas Montange, Rejane Rua, Antoine GessainAbstract: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+, and CD19+ lymphocyte samples and rarely in CD14+ monocyte and CD56+ NK lymphocyte samples. The median (interquartile range [IQR]) SFV DNA counts were 16.0 (11.0 to 49.8), 11.3 (5.9 to 28.3), and 17.2 (2.0 to 25.2) copies/105 cells in CD8+ T lymphocytes, CD4+ T lymphocytes, and CD19+ B lymphocytes, respectively. In the CD4 compartment, SFV DNA was detected in both memory and naive CD4+ T lymphocytes. SFV DNA levels in 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.
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RESEARCH Open Access
2013Co-Authors: Augustin Mouinga-ondémé, Bettina Salle, Edouard Betsem, Melanie Caron, Noemie Renault, Paul Telfer, Maria Makuwa, Ali Saïb, Preston Marx, Antoine GessainAbstract:Two distinct variants of Simian Foamy Virus in naturally infected mandrills (Mandrillus sphinx) and cross-species transmission to humans Mouinga-Ondémé et al
William M. Switzer - One of the best experts on this subject based on the ideXlab platform.
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human t cell lymphotropic Virus type 1 transmission dynamics in rural villages in the democratic republic of the congo with high nonhuman primate exposure
PLOS Neglected Tropical Diseases, 2021Co-Authors: Megan Halbrook, Anupama Shankar, Haoqiang Zheng, Ellsworth M Campbell, Adva Gadoth, Nicole A Hoff, Jeanjacques Muyembe, Emile Okitolonda Wemakoy, Anne W Rimoin, William M. SwitzerAbstract:The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to Simian retroViruses yet little is known about the extent of zoonotic Simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic Viruses (HTLV), a retroVirus group of Simian origin, in a large population of persons with frequent NHP exposures and a history of Simian Foamy Virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and Simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen's swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with Simian Foamy Virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity.
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Complete Genome Sequence of a Baboon Simian Foamy Virus Isolated from an Infected Human.
Microbiology resource announcements, 2020Co-Authors: Anupama Shankar, Vedapuri Shanmugam, William M. SwitzerAbstract:ABSTRACT We obtained the full-length genome of a Simian Foamy Virus (SFV) from an infected human. This Virus originated from a baboon (Papio species, strain SFVpxx_hu9406). The genome is 13,113 nucleotides long with the canonical SFV genome structure. Phylogenetically, SFVpxx_hu9406 clustered closely with SFVpan_V909/03F from a captive baboon and other Cercopithecidae SFVs.
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bayesian inference reveals ancient origin of Simian Foamy Virus in orangutans
Infection Genetics and Evolution, 2017Co-Authors: Michael J C Reid, William M. Switzer, Michael A Schillaci, Amy R Klegarth, Ellsworth M Campbell, Manon Ragonnetcronin, Isabelle Joanisse, Kyna Caminiti, Carl LowenbergerAbstract:Simian Foamy Viruses (SFVs) infect most nonhuman primate species and appears to co-evolve with its hosts. This co-evolutionary signal is particularly strong among great apes, including orangutans (genus Pongo). Previous studies have identified three distinct orangutan SFV clades. The first of these three clades is composed of SFV from P. abelii from Sumatra, the second consists of SFV from P. pygmaeus from Borneo, while the third clade is mixed, comprising an SFV strain found in both species of orangutan. The existence of the mixed clade has been attributed to an expansion of P. pygmaeus into Sumatra following the Mount Toba super-volcanic eruption about 73,000years ago. Divergence dating, however, has yet to be performed to establish a temporal association with the Toba eruption. Here, we use a Bayesian framework and a relaxed molecular clock model with fossil calibrations to test the Toba hypothesis and to gain a more complete understanding of the evolutionary history of orangutan SFV. As with previous studies, our results show a similar three-clade orangutan SFV phylogeny, along with strong statistical support for SFV-host co-evolution in orangutans. Using Bayesian inference, we date the origin of orangutan SFV to >4.7 million years ago (mya), while the mixed species clade dates to approximately 1.7mya, >1.6 million years older than the Toba super-eruption. These results, combined with fossil and paleogeographic evidence, suggest that the origin of SFV in Sumatran and Bornean orangutans, including the mixed species clade, likely occurred on the mainland of Indo-China during the Late Pliocene and Calabrian stage of the Pleistocene, respectively.
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dual Simian Foamy Virus human immunodeficiency Virus type 1 infections in persons from cote d ivoire
PLOS ONE, 2016Co-Authors: William M. Switzer, Anupama Shankar, Shaohua Tang, Haoqiang Zheng, Vickie Sullivan, Timothy C. Granade, Patrick Sprinkle, Walid HeneineAbstract:Zoonotic transmission of Simian retroViruses in West-Central Africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency Viruses (HIVs) and human T-lymphotropic Viruses (HTLVs). While Simian Foamy Virus (SFV) and Simian T- lymphotropic Virus (STLV)-like infection were reported in healthy persons exposed to nonhuman primates (NHPs) in West-Central Africa, less is known about the distribution of these Viruses in Western Africa and in hospitalized populations. We serologically screened for SFV and STLV infection using 1,529 specimens collected between 1985 and 1997 from Cote d'Ivoire patients with high HIV prevalence. PCR amplification and analysis of SFV, STLV, and HIV/SIV sequences from PBMCs was used to investigate possible Simian origin of infection. We confirmed SFV antibodies in three persons (0.2%), two of whom were HIV-1-infected. SFV polymerase (pol) and LTR sequences were detected in PBMC DNA available for one HIV-infected person. Phylogenetic comparisons with new SFV sequences from African guenons showed infection likely originated from a Chlorocebus sabaeus monkey endemic to Cote d'Ivoire. 4.6% of persons were HTLV seropositive and PCR testing of PBMCs from 15 HTLV seroreactive persons identified nine with HTLV-1 and one with HTLV-2 LTR sequences. Phylogenetic analysis showed that two persons had STLV-1-like infections, seven were HTLV-1, and one was an HTLV-2 infection. 310/858 (53%), 8/858 (0.93%), and 18/858 (2.1%) were HIV-1, HIV-2, and HIV-positive but undifferentiated by serology, respectively. No SIV sequences were found in persons with HIV-2 antibodies (n = 1) or with undifferentiated HIV results (n = 7). We document SFV, STLV-1-like, and dual SFV/HIV infection in Cote d'Ivoire expanding the geographic range for zoonotic Simian retroVirus transmission to West Africa. These findings highlight the need to define the public health consequences of these infections. Studying dual HIV-1/SFV infections in immunocompromised populations may provide a new opportunity to better understand SFV pathogenicity and transmissibility in humans.
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Inference of the evolutionary history of human infection with Simian Foamy Virus (SFV).
2016Co-Authors: William M. Switzer, Anupama Shankar, Shaohua Tang, Haoqiang Zheng, Patrick S. Sprinkle, Vickie Sullivan, Timothy C. Granade, Walid HeneineAbstract:A. Bayesian SFV polymerase (pol) maximum clade credibility tree inferred using an alignment of 375-bp and 88 Old World monkey and ape taxa, including 26 new African green monkey sequences (in blue text). The SFV pol sequence from the Côte d’Ivoire patient, LDAA-04731, is shown in green text. B. Chlorocebus mitochondrial DNA phylogenetic relationships inferred by Bayesian analysis of an alignment of 496-bp from 65 taxa. New sequences generated in our study are highlighted in blue text. Animal country of origin given at end of taxa names; CAR = Central African Republic, Unk = provenance unknown. Csa, Chl. sabaeus, Cae, Chl. aethiops, Cta, Chl. tantalus, Cpy, Chl. pygerythrus, Ccy, Chl. cynosuros. Posterior probabilities > 0.7 are given at major nodes in the tree. Scale bar is in units of time.