Neutralization of zoonotic retroviruses by human antibodies: Genotype-specific epitopes within the receptor-binding domain from simian foamy virus.

Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs. Trial registration: The study was registered at www.clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03225794/.

Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus.

We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.

High seroreactivities to orthoebolaviruses in rural Cameroon: a case-control study on non-human primate bites and a cross-sectional survey in rural population.

BACKGROUND: Ebola (EBOV) and Sudan (SUDV) orthoebolaviruses are responsible for lethal haemorrhagic fever outbreaks in humans in Central and West Africa, and in apes that can be at the source of human outbreaks for EBOV. METHODS: To assess the risk of exposure to orthoebolaviruses through contact with non-human primates (NHP), we tested the presence of antibodies against different viral proteins with a microsphere-based multiplex immunoassay in a case-control study on bites from NHPs in forest areas from Cameroon (n=795), and in cross-sectional surveys from other rural populations (n=622) of the same country. RESULTS: Seroreactivities against at least two viral proteins were detected in 13% and 12% of the samples for EBOV and SUDV, respectively. Probability of seroreactivity was not associated with history of NHP bites, but was three times higher in Pygmies compared to Bantus. Although no neutralizing antibodies to EBOV and SUDV were detected in a selected series of highly reactive samples, avidity results indicate strong affinity to SUDV antigens. CONCLUSION: The detection of high level of seroreactivities against orthoebolaviruses in rural Cameroon where no outbreaks have been reported, raises the possibilities of silent circulation of orthoebolavirus, or of other not yet documented filoviruses, in these forested regions.

Concurrent Clade I and Clade II Monkeypox Virus Circulation, Cameroon, 1979-2022.

During 1979-2022, Cameroon recorded 32 laboratory-confirmed mpox cases among 137 suspected mpox cases identified by the national surveillance network. The highest positivity rate occurred in 2022, indicating potential mpox re-emergence in Cameroon. Both clade I (n = 12) and clade II (n = 18) monkeypox virus (MPXV) were reported, a unique feature of mpox in Cameroon. The overall case-fatality ratio of 2.2% was associated with clade II. We found mpox occurred only in the forested southern part of the country, and MPXV phylogeographic structure revealed a clear geographic separation among concurrent circulating clades. Clade I originated from eastern regions close to neighboring mpox-endemic countries in Central Africa; clade II was prevalent in western regions close to West Africa. Our findings suggest that MPXV re-emerged after a 30-year lapse and might arise from different viral reservoirs unique to ecosystems in eastern and western rainforests of Cameroon.

Plasma antibodies from humans infected with zoonotic simian foamy virus do not inhibit cell-to-cell transmission of the virus despite binding to the surface of infected cells.

Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at least in vitro, despite their capacity to bind to the surface of infected cells. Trial registration: Clinical trial registration: www.clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03225794/.

First detection of Rift Valley fever virus antibodies in non-human primates in Cameroon.

We tested for Rift Valley fever virus (RVFV) from at least 15 species of non-human primates. RVFV IgG/IgM antibodies were detected in 3.7% (2 out of 53) of chimpanzees (Pan troglodytes) and in 1.4% (1 out of 72) of unidentified non-human primate species. This study was the first investigation of RVFV in monkeys in Cameroon.

A decade-long retrospective study of hepatitis C virus genetic diversity in Cameroon, 2013-2023: presence of a high proportion of unsubtypable and putative recombinant HCV strains.

While treatment options for hepatitis C virus (HCV) infection have expanded considerably over the past decade thanks to the development of pan-genotypic therapies, genotype testing remains a prerequisite for treatment in sub-Saharan African countries, including Cameroon, where multiple HCV genotypes and subtypes exist. The main objective of this study was to describe the trend in the distribution of HCV genotypes and subtypes from 2013 to 2023 in the Cameroonian population. Viral loads were determined using the Abbott real-time assay, and genotyping/subtyping was based on nested and semi-nested reverse transcription polymerase chain reaction (RT-PCR) amplification of the regions encoding the core and non-structural protein 5B (NS5B) regions, respectively, followed by sequencing and phylogenetic analysis. A total of 512 patients with NS5B and core sequencing results were included in our study. Genotyping revealed a predominance of both genotype 4 (38.48%) and genotype 1 (37.11%), followed by genotype 2, detected in 22.46% of patients. Interestingly, 10 samples (1.95%) had discordant genotypes in both regions, suggesting the presence of putative recombinant forms of HCV. Twelve different subtypes were detected during the study period, with a predominance of subtypes 4f (18.95%) and 1e (16.02%). Furthermore, phylogenetic analysis failed to assign a subtype to a relatively high proportion of sequences (38.67%) for the two genomic regions, and their classification was limited to genotype assignment. The frequency distribution of HCV genotypes did not show any statistical difference according to year or sex. These results confirm the genetic diversity of HCV in Cameroon and the potential for the generation of recombinant strains.

Evaluation of the mpox surveillance system in Cameroon from 2018 to 2022: a laboratory cross-sectional study.

BACKGROUND: Formal assessment of a surveillance system's features and its ability to achieve objectives is crucial for disease control and prevention. Since the implementation of the mpox surveillance system in Cameroon, no evaluation has been conducted. METHODS: In a cross-sectional study, we assessed the performance of the mpox surveillance system in accordance with the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) guidelines. We collected mpox surveillance data from 2018 to 2022 and conducted a survey with key stakeholders of the surveillance program. The survey results were summarized. The rates of complete reporting and mpox detection, as well as the time lag between the different stages of surveillance were analyzed using R version 4.1. RESULTS: The mpox detection rate was 21.6% (29/134) over the five years under review. Surveillance indicators revealed that a combination of sample types, including vesicles, crust, and blood, was associated with higher case confirmation. Overall, the mpox surveillance system was effective. Weaknesses in terms of simplicity were identified. Most components of the assessed system failed to meet the timeliness and data quality goals, except for the laboratory component, which was commendable. The lack of a computerized shared database and the system's non-sustainability were a course of concern. CONCLUSIONS: Despite all identified bottlenecks in the mpox surveillance system in Cameroon, it was found to meet it stipulated goals. Recommendations are made for training on surveillance system features, particularly at the facility/field level. Therefore, there is a crucial need to globally improve the mpox surveillance system in Cameroon for better disease control.

Impact of the 2022 African Cup of Nations mass-gathering event on the COVID-19 epidemic in Garoua, Cameroon.

BACKGROUND: The 2022 African Cup of Nations (AFCON) took place in Cameroon from January 9th to February 5th, 2022, including Garoua in the north. We aimed to measure the impact of this event on the local COVID-19 epidemic given the implementation of a preventive strategy based on a health pass. METHODS: All players, staff and fans involved in the AFCON event were screened with PCR tests. Symptomatic cases were also continuously monitored in the general population and screened for variants of concern. Daily numbers of confirmed cases were compared to neighboring countries numbers retrieved from a public domain source. RESULTS: In total, 1479 and 2481 tests were performed in the general population and on asymptomatic AFCON attendees, respectively. From the latter, 12.5% were PCR-positive; 97% were infected with Omicron, with no significant difference compared to the passive program (G-test, P value = 0.162). Surveillance indicated the AFCON did not increase the number of symptomatic PCR-positive cases in the general population compared to neighboring countries. CONCLUSIONS: Though the COVID-19 epidemic was fueled by asymptomatic cases infected with the Omicron variant at the time, the non-therapeutic preventive measures implemented for AFCON mitigated an increase in the epidemic in the local population.

Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa.

BACKGROUND: Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. METHODS: From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. RESULTS: Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7-1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3-6.2), history of surgery (aOR, 6.3; 95% CI, 2.2-17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2-19.8). CONCLUSIONS: These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.

Epidemiology of rotavirus in humans, animals, and the environment in Africa: a systematic review and meta-analysis.

INTRODUCTION: Globally, rotavirus infections are the most common cause of diarrhea-related deaths, especially among children under 5 years of age. This virus can be transmitted through the fecal-oral route, though zoonotic and environmental contributions to transmission are poorly defined. The purpose of this study is to determine the epidemiology of rotavirus in humans, animals, and the environment in Africa, as well as the impact of vaccination. METHODS: We searched PubMed, Web of Science, Africa Index Medicus, and African Journal Online, identifying 240 prevalence data points from 224 articles between 2009 and 2022. RESULTS: Human rotavirus prevalence among patients with gastroenteritis was 29.8% (95% CI, 28.1-31.5; 238710 participants), with similar estimates in children under 5 years of age, and an estimated case fatality rate of 1.2% (95% CI, 0.7-2.0; 10440 participants). Prevalence was estimated to be 15.4% and 6.1% in patients with non-gastroenteritis illnesses and apparently healthy individuals, respectively. Among animals, prevalence was 9.3% (95% CI, 5.7-13.7; 6115 animals), and in the environmental water sources, prevalence was 31.4% (95% CI, 17.7-46.9; 2530 samples). DISCUSSION: Our findings highlight the significant burden of rotavirus infection in Africa, and underscore the need for a One Health approach to limiting the spread of this disease.

APOBEC3C S188I Polymorphism Enhances Context-Specific Editing of Hepatitis B Virus Genome.

Single-nucleotide polymorphism in APOBEC3C (resulting in a serine to isoleucine in position 188) is present in approximately 10% of African populations and greatly enhances restriction against human immunodeficiency virus-1 and simian immunodeficiency virus by improving dimerization and DNA processivity of the enzyme. In this study, we demonstrated in culture and in infected patients that hepatitis B virus (HBV) could be edited by APOBEC3CS188I. Using next-generation sequencing, we demonstrated that APOBEC3CS188I led to enhanced editing activity in 5'TpCpA→5'TpTpA context. This constitutes a new hallmark of this enzyme, which could be used to determine its impact on HBV or nuclear DNA.

Maternal Age at First Childbirth and Geographical Variation in Hepatitis B Virus Prevalence in Cameroon: Important Role of Mother-to-Child Transmission.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection varies geographically around the world. Yet, its underlying mechanisms are unknown. Using a nationally representative population-based sample from all 58 administrative divisions in Cameroon, we examined the association between median maternal age at first childbirth in a preceding generation, a proxy for the frequency of mother-to-child transmission (MTCT) of HBV in a region, and the risk of chronic HBV infection, defined as positive surface antigen (HBsAg), in the index generation. METHODS: We estimated a division-specific median maternal age at first childbirth using Demographic Health Surveys (DHSs) conducted in 1991, 1998, 2004, and 2011. We tested HBsAg in 2011 DHS participants. We used maps to display spatial variation. RESULTS: In 14 150 participants (median age, 27 years; 51% females), the overall weighted prevalence of HBsAg was 11.9% (95% confidence interval [CI], 11.0 to 12.8), with a wide geographical variation across the divisions (range, 6.3%-23.7%). After adjusting for confounders and spatial dependency, lower maternal age at first childbirth was significantly associated with positive HBsAg at the division level (ß, 1.89; 95% CI, 1.26 to 2.52) and at the individual level (odds ratio, 1.20; 95% CI, 1.04 to 1.39). A similar ecological correlation was observed across other African countries. CONCLUSIONS: The significant association between the maternal age at first childbirth and HBsAg positivity suggests a crucial role of MTCT in maintaining high HBV endemicity in some areas in Cameroon. This underlines an urgent need to effectively prevent MTCT in sub-Saharan Africa.

Molecular characterization of chikungunya virus from the first cluster of patients during the 2020 outbreak in Chad.

We sequenced a portion of the E1 envelope protein gene of two of four CHIKV RT-PCR-positive samples from the first cluster of chikungunya patients during the 2020 Chad outbreak. Phylogenetic analysis revealed that the viruses belonged to the East/Central/South/African genotype but lacked the E1 A226V and K211E mutations associated with viral adaptability and transmission, suggesting an autochthonous transmission. These sequences are a useful basis for tracking viral evolution in subsequent outbreaks in Chad.

Sustained circulation of yellow fever virus in Cameroon: an analysis of laboratory surveillance data, 2010-2020.

BACKGROUND: The re-emergence of yellow fever poses a serious public health risk to unimmunized communities in the tropical regions of Africa and South America and unvaccinated travelers visiting these regions. This risk is further accentuated by the likely spread of the virus to areas with potential for yellow fever transmission such as in Asia, Europe, and North America. To mitigate this risk, surveillance of yellow fever is pivotal. We performed an analysis of laboratory-based surveillance of yellow fever suspected cases in Cameroon during 2010-2020 to characterize the epidemiology of yellow fever cases and define health districts at high risk. METHOD: We reviewed IgM capture ELISA and plaque reduction neutralization test (PRNT) test results of all suspected yellow fever patients analyzed at Centre Pasteur of Cameroon, the national yellow fever testing laboratory, during 2010-2020. RESULTS: Of the 20,261 yellow fever suspected patient's samples that were tested, yellow fever IgM antibodies were detected in 360 patients representing an annual average of 33 cases/year. A major increase in YF IgM positive cases was observed in 2015 and in 2016 followed by a decrease in cases to below pre-2015 levels. The majority of the 2015 cases occurred during the latter part of the year while those in 2016, occurred between February and May. This trend may be due to an increase in transmission that began in late 2015 and continued to early 2016 or due to two separate transmission events. In 2016, where the highest number of cases were detected, 60 health districts in the 10 regions of Cameroon were affected with the Littoral, Northwest and, Far North regions being the most affected. After 2016, the number of detected yellow fever IgM positive cases dropped. CONCLUSION: Our study shows that yellow fever transmission continues to persist and seems to be occurring all over Cameroon with all 10 regions under surveillance reporting a case. Preventive measures such as mass vaccination campaigns and routine childhood immunizations are urgently needed to increase population immunity. The diagnostic limitations in our analysis highlight the need to strengthen laboratory capacity and improve case investigations.

First molecular characterization of the hepatitis E virus in humans in Cameroon: Confirmation of the HEV outbreak in Touboro, North-Cameroon.

Hepatitis E virus (HEV) is a major causative agent of acute viral hepatitis in many regions of the world including Africa. In Cameroon, there is no published molecular study on HEV in humans. However, based on serological assays, the first outbreak of HEV was detected in North-Cameroon. The objective of this study was to determine the molecular characterization of HEV that circulated during this period. A retrospective study design was used to select serum samples among those collected during the outbreak period. immunoglobulin M positive samples available in sufficient volumes to amplify HEV RNA were selected. RNA was extracted and then amplified by a real-time reverse transcription polymerase chain reaction (real time RT-PCR) assay, followed by a nested reverse transcription polymerase chain reaction (nested RT-PCR) assay for sequencing and phylogenetic analysis. Overall, 24 samples were selected and HEV RNA was amplified by real-time RT-PCR in 20 samples. Amongst these, 12 samples were positive for HEV RNA by nested RT-PCR and yielded good sequencing products. Phylogenetic analysis showed that 10 samples clustered with HEV genotype 1 (subtype 1e) and two samples clustered with HEV genotype 3 (subtype 3f). This study fills the gap of knowledge on the molecular epidemiology of HEV in Cameroon and confirms the first report of the hepatitis E outbreak in North-Cameroon.

Epidemiology of hepatitis E virus infection in animals in Africa: a systematic review and meta-analysis.

BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute hepatitis in humans worldwide and have high burden in the resource-limited countries. Better knowledge of the epidemiology of hepatitis in animals in Africa can help to understand the epidemiology among humans. The objective of this study was to summarize the prevalence of HEV infection and distribution of HEV genotypes among animals in Africa. METHODS: In this systematic review and meta-analysis, we comprehensively searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to March 22th, 2020 without any language restriction. We considered cross-sectional studies of HEV infection in animals in Africa. Study selection, data extraction, and methodological quality of included studies were done independently by two investigators. Prevalence data were pooled using the random-effects meta-analysis. This review was registered in PROSPERO, CRD42018087684. RESULTS: Twenty-five studies (13 species and 6983 animals) were included. The prevalence (antibodies or ribonucleic acid [RNA]) of HEV infection in animals varied widely depending on biological markers of HEV infection measured: 23.4% (95% confidence interval; 12.0-37.2) for anti-HEV immunoglobulins G, 13.1% (3.1-28.3) for anti-HEV immunoglobulins M, and 1.8% (0.2-4.3) for RNA; with substantial heterogeneity. In subgroup analysis, the immunoglobulins G seroprevalence was higher among pigs 37.8% (13.9-65.4). The following HEV genotypes were reported in animals: Rat-HEV genotype 1 (rats and horses), HEV-3 (pigs), HEV-7 (dromedaries), and Bat hepeviruses (bats). CONCLUSIONS: We found a high prevalence of HEV infection in animals in Africa and HEV genotypes close to that of humans. Some animals in Africa could be the reservoir of HEV, highlighting the need of molecular epidemiological studies for investigating zoonotic transmission.

Case-Control Study of the Immune Status of Humans Infected With Zoonotic Gorilla Simian Foamy Viruses.

BACKGROUND: Zoonotic simian foamy viruses (SFVs) establish persistent infections in humans, for whom the long-term consequences for health are poorly described. In this study, we aimed to characterize blood-cell phenotypes and plasma biomarkers associated with gorilla SFV infection in humans. METHODS: We used a case-control design to compare 15 Cameroonian hunters infected with gorilla SFV (cases) to 15 controls matched for age and ethnicity. A flow cytometry-based phenotypic study and quantification of plasma immune biomarkers were carried out on blood samples from all participants. Wilcoxon signed-rank tests were used to compare cases and controls. RESULTS: Cases had a significantly higher percentage of CD8 T lymphocytes than controls (median, 17.6% vs 13.7%; P = .03) but similar levels of B, natural killer, and CD4 T lymphocytes. Cases also had a lower proportion of recent CD4 thymic emigrants (10.9% vs 18.6%, P = .05), a higher proportion of programmed death receptor 1 (PD-1) expressing memory CD4 T lymphocytes (31.7% vs 24.7%, P = .01), and higher plasma levels of the soluble CD163 scavenger receptor (0.84 vs .59 µg/mL, P = .003) than controls. CONCLUSIONS: We show, for the first time, that chronic infection with SFV is associated with T lymphocyte differentiation and monocyte activation.

The epidemiology of hepatitis delta virus infection in Cameroon.

OBJECTIVE: To investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon. DESIGN: We tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies. RESULTS: Overall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15-49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work). CONCLUSION: We found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.

An Immunodominant and Conserved B-Cell Epitope in the Envelope of Simian Foamy Virus Recognized by Humans Infected with Zoonotic Strains from Apes.

Cross-species transmission of simian foamy viruses (SFVs) from nonhuman primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently nonpathogenic in vivo, with ubiquitous in vitro tropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, or Cercopithecus SFV). We demonstrate the specific recognition of peptide N96-V110 located in the leader peptide, gp18LP Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N96-V110 was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with a Cercopithecus SFV. In conclusion, we have been the first to define an immunodominant B-cell epitope recognized by humans following zoonotic SFV infection.IMPORTANCE Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18LP, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.