HUMAN FOAMY VIRUS REVERSE TRANSCRIPTION THAT OCCURS LATE IN THE VIRALREPLICATION CYCLE

Foamy viruses (FVs) are retroid viruses which use a replication strate gy unlike those of other retroviruses and hepadnaviruses (S, F. Yu, D, N. Baldwin, S, R, Gwynn, S, Yendapilli, and M. L. Linial, Science 271 :1579-1582, ,1996), One of the striking differences between FVs and re troviruses is the presence of large amounts of linear genome-length DN A in FV-infected cells and in virions. We report here that large quant ities of genome-length linear FV DNA accumulate in cells infected with n', as determined by Southern blotting, To determine whether these un integrated virus DNAs result solely from superinfection, we analyzed t he occurrence of virus cDNA of the so-called human FV isolate (HFV) in cells transfected with a virus mutant deficient in the envelope gene and in cells which are resistant to superinfection due to stable expre ssion of the envelope protein, We show that the synthesis of viral cDN A is independent of superinfection and that HEV synthesizes cDNA intra cellularly as a late event in the replication cycle, To further confir m this finding, we performed inhibition studies with the reverse trans criptase inhibitor zidovudine (AZT), While AZT had no effect or only a minor effect on virus titers when added to cells prior to virus infec tion, viral titers were reduced by 3 or 4 orders of magnitude when the virus was produced from cells in the presence of AZT. Our results are most compatible with the hypothesis that the functional nucleic acid of the extracellular HFV consists of largely double-stranded linear DN A.