New World Simian Foamy Virus Infections In Vivo and In Vitro

Abstract

e Foamy viruses (FV) are complex retroviruses that naturally infect all nonhuman primates (NHP) studied to date. Zoonotic transmission of Old World NHP simian foamy viruses (SFV) has been documented, leading to nonpathogenic persistent infections. To date, there have been no reports concerning zoonotic transmission of New World monkey (NWM) SFV to humans and resulting infection. In this study, we developed a Western blot assay to detect antibodies to NWM SFV, a nested PCR assay to detect NWM SFV DNA, and a ␤-galactosidase-containing indicator cell line to assay replication of NWM SFV. Using these tools, we analyzed the plasma and blood of 116 primatologists, of whom 69 had reported exposures to NWM. While 8 of the primatologists tested were seropositive for SFV from a NWM, the spider monkey, none had detectable levels of viral DNA in their blood. We found that SFV isolated from three different species of NWM replicated in some, but not all, human cell lines. From our data, we conclude that while humans exposed to NWM SFV produce antibodies, there is no evidence for long-term viral persistence. Foamy viruses (FV) are unusual complex retroviruses that infect cattle, horses, cats, and all species of nonhuman primates (NHP) examined to date (reviewed in reference 1). Simian foamy viruses (SFV) can cause life-long infections in natural hosts without any apparent pathogenicity (2). In cell culture models, SFV can establish latent infections in some cell types and lytic infections in others, resulting in cytopathic effects (CPE) that include syncytium formation (reviewed in reference 3). In infected macaques, FV DNA is found in almost all tissues, while FV RNA and replicating virus are limited to the superficial epithelial cells of the oral mucosa in immunocompetent animals (4, 5). Consistent with the site of viral replication detected in vivo, it is thought that FV are transmitted via saliva, through grooming, biting, and other behaviors. Studies of natural transmission suggest that infant and young NHP are resistant to infection, presumably because of passive immunity from maternal antibodies, but typically (for macaques) become infected by 3 years of age (6). Epidemiological studies indicate that SFV seroprevalence can reach up to 100% in adults (reviewed in reference 7).Although FV do not naturally infect humans, SFV have been found to be zoonotically transmitted, most likely through contact with saliva from an infected NHP. Several studies have documented the transmission of SFV to humans who interact directly with Old World (OW) NHP, including Cercopithicus species, baboons, macaques, mandrills, gorillas, and chimpanzees (reviewed in reference 7). SFV antibody-positive humans have been found in a variety of natural settings, including people in Asia who live in areas with free-ranging macaques, villagers in Gabon with known exposure to NHP, and a population of hunters in Cameroon with bites from Old World NHP (6,(8)(9)(10)(11). SFV antibody-positive humans have also been documented in various laboratory, veterina...

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

“…Thus, the lower antibody response to Cercopithecus SFV than to ape SFV in humans may be indirect evidence for lower replication levels of Cercopithecus SFV during either the primary or the chronic phase of the infection. This is consistent with lower rates of SFV DNA detection in individuals infected with macaque SFV than for those infected with ape SFV and the absence of such DNA in humans infected with NWM SFV (3,5,12,31). An alternative explanation could be lower immunogenicity of Cercopithecus SFV than that of ape SFV.…”

“…studies carried out worldwide (1,2). Human exposure to SFV from New World monkeys (NWM) leads to SFV-specific seroreactivity, with undetectable blood SFV DNA (3,4). Almost all SFV-infected individuals were bitten or injured by a NHP, and no case of human-to-human SFV transmission has yet been reported (1,2,5).…”

A new sensitive indicator cell line reveals cross-transactivation of the viral LTR by gorilla and chimpanzee simian foamy viruses

“…The quantitative bioassay of viruses based on functional detection of an early synthesized viral protein is efficient for the detection of gorilla SFVs, consistent with results obtained with FV from several mammalian species (Jones-Engel et al, 2007;Stenbak et al, 2014;Zemba et al, 2000). Parallel titration showed similar sensitivity of GFAB and FAB cells for the quantification of chimpanzee SFVs, and a higher sensitivity of GFAB cells for the quantification of gorilla SFVs.…”

Eleventh International Foamy Virus Conference—Meeting Report

“…These data suggest that NWM SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses, but without evidence of persistent infection in peripheral blood. Interestingly, quite similar results were obtained in a recently published work by a US team [12]. …”