In Asia, contact between persons and nonhuman primates is widespread in multiple occupational and nonoccupational contexts. Simian foamy viruses (SFVs) are retroviruses that are prevalent in all species of nonhuman primates. To determine SFV prevalence in humans, we tested 305 persons who lived or worked around nonhuman primates in several South and Southeast Asian countries; 8 (2.6%) were confi rmed SFV positive by Western blot and, for some, by PCR. The interspecies interactions that likely resulted in virus transmission were diverse; 5 macaque taxa were implicated as the source of infection. Phylogenetic analysis showed that SFV from 3 infected persons was similar to that from the nonhuman primate populations with which the infected persons reported contact. Thus, SFV infections are likely to be prevalent among persons who live or work near nonhuman primates in Asia.

Foamy viruses (FV) are retroviruses that naturally infect many hosts, including most nonhuman primates (NHPs). Zoonotic infection by primate FV has been documented in people inAsia who reported contact with free-ranging macaques. FV transmission in Asia is a concern, given abundant human-NHP contact, particularly at monkey temples and in urban settings. We have developed three assays capable of detecting the presence of FV in Asian NHP species that are commensal with humans: enzyme-linked immunosorbent assay (ELISA), Western blot assays using recombinant viral Gag protein, and an indicator cell line that can detect macaque FV. The recombinant ELISA correlates very well with the presence of FV sequences detected by PCR. We have used these assays to demonstrate both that FV is highly prevalent among free-ranging NHPs and that seroconversion occurs at a young age in these animals. These assays should also prove useful for large-scale analysis of the prevalence of FV infections in human populations in Asia that are commensal with free-ranging NHPs.Foamy viruses (FV) comprise a subfamily of retroviruses (22). FV were first identified over 50 years ago (10) as contaminants in monkey tissue culture explants. They are highly cytopathic in tissue culture. Infection of a number of cell types, including fibroblasts and epithelial cells, leads to rapid syncytium formation, vacuolization, and cell death. Despite this, infection in animal hosts does not produce a recognized disease state. Rather, FV establish a persistent asymptomatic infection in both natural and zoonotic hosts (reviewed in reference 23). Although proviral DNA can be found in nearly every tissue, indicating infection, the virus only replicates to a detectable level in the oral mucosa. Replication at this site facilitates transfer to other hosts through saliva (26). Although it is not known how latency is maintained in vivo, an in vitro latency model has been described in which viral replication is controlled at the transcriptional level (24).FV are widespread and have been isolated from a variety of nonprimate species, including cows, cats, and horses (reviewed in reference 27). All nonhuman primates (NHPs) examined to date, including gorillas, chimpanzees, orangutans, baboons, African green monkeys, and macaques (reviewed in reference 12) also harbor FV, called simian foamy viruses (SFV). Infection among captive populations of NHPs is high. Studies from captive and free-ranging populations show that up to 100% of adult NHPs are infected with SFV (2,7,8,16,17,19). Curiously, despite its widespread infection among NHPs, evidence suggests that there is no human-specific FV (reviewed in reference 23). A single report describing HFV (human foamy virus) in a tissue culture that was derived from a Kenyan man (1) is now believed to represent a zoonotic transmission of SFV from chimpanzees (32). There are several reports of zoonotic transmission of SFV from various taxa of NHPs. Many of the infected individuals, such as zoo keepers and animal care workers, had frequ...

The foamy virus (FV) genome contains two promoters, the canonical long terminal repeat (LTR) promoter, containing three consensus AP-1 binding sites, and an internal promoter (IP) within the env gene. We investigated the regulation of the two promoters in lytic and persistent infections and found that in the presence of a constitutive source of the viral transactivator protein Tas, transactivation of the LTR promoter and that of the IP differ. In lytic infections, both the LTR promoter and the IP are efficiently transactivated by Tas, while in persistent infections, the IP is efficiently transactivated by Tas, but the LTR promoter is not. Analysis of proteins expressed from the LTR promoter and the IP during infection indicated that IP transcription is more robust than that of the LTR promoter in persistently infected cells, while the opposite is true for lytically infected cells. Coculture experiments also showed that LTR promoter transcription is greatest in cells which support lytic replication. Replacement of much of the LTR promoter with the IP leads to increased viral replication in persistent but not lytic infections. We also found that the induction of persistently infected cells with phorbol 12-myristate 13-acetate (PMA) greatly enhanced viral replication and transcription from the SFVcpz(hu) (new name for human FV) LTR promoter. However, mutation of three consensus AP-1 binding sites in the FV LTR promoter did not affect viral replication in lytically or persistently infected cells, nor did the same mutations affect LTR promoter transactivation by Tas in PMA-treated cells. Our data indicate that differential regulation of transcription is important in the outcome of FV infection but is unlikely to depend on AP-1.Foamy viruses (FVs) are unique among retroviruses in their establishment of life-long persistent infections without any accompanying pathologies. Infection is characterized by the presence of viral DNA in a large number of organs (9, 42), without detectable levels of viral RNA or protein expression (6,9,42,44). Indeed, viral transcription has been detected only in the oral mucosa of a single infected animal (9). However, virus can be recovered readily by coculturing of infected tissues, peripheral blood, or throat swab specimens with susceptible cell lines (6,18,42,44,46,49). Thus, in most locations in vivo, FV replication is latent; however, when the virus is removed from such a context, replication can proceed. In contrast to the in vivo situation, FV replication in vitro can result in either lytic or persistent infection (13,41,53). Infection of many cell types in vitro is often accompanied by cytopathic effects (CPE) and rapid cell killing. Since such infections do not mimic the in vivo situation, we sought to develop a tissue culture system in which there is little viral replication. For these studies we used the prototypic human FV (HFV) clone HFV13 (29). HFV has recently been renamed SFVcpz(hu) to more clearly indicate that the original HFV isolate is a chimpanzee FV isolated from a huma...