Persistent zoonotic infection of a human with simian foamy virus in the absence of an intact orf-2 accessory gene

Although foamy viruses (FVs) are endemic among nonhuman primates, FV infect ion among humans is rare. Recently, simian foamy virus (SFV) infection was reported in 4 of 231 individuals occupationally exposed to primates (1.8%). Secondary transmission to spouses has not been seen, suggesting that while FV is readily zoonotic, humans may represent dead-end hosts. Among differe nt simian species, SFV demonstrates significant sequence diversity within t he U3 region of the long terminal repeat (LTR) and 3' accessory open readin g frames (ORFs). To examine if persistent human SFV infection and apparent lack of secondary transmission are associated with genetic adaptations in F V regulatory regions, we conducted sequence analysis of the LTR, internal p romoter, ORF-1, and ORF-2 on a tissue culture isolate and peripheral blood mononuclear cell samples from a human infected with SFV of African green mo nkey origin (SFV-3). Compared to the prototype SFV-3 sequence, the LTR, int ernal promoter, and FV transactivator (ORF-1) showed sequence conservation, suggesting that FV zoonosis is not dependent on host-specific adaptation t o these transcriptionally important regions. However, ORF-2 contains a numb er of deleterious mutations predicted to result in premature termination of protein synthesis. ORF-2 codes in part for the 60-kDa Bet fusion protein, proposed to be involved in the establishment of persistent cellular SFV inf ections. These results suggest that persistent human infection by SFV and r educed transmissibility may be influenced by the absence of a functional OR F-2.