Human foamy virus reverse transcription that occurs late in the viral replication cycle

Abstract

Foamy viruses (FVs) are retroid viruses which use a replication strategy 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 retroviruses is the presence of large amounts of linear genome-length DNA in FV-infected cells and in virions. We report here that large quantities of genome-length linear FV DNA accumulate in cells infected with FV, as determined by Southern blotting. To determine whether these unintegrated virus DNAs result solely from superinfection, we analyzed the 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 expression of the envelope protein. We show that the synthesis of viral cDNA is independent of superinfection and that HFV synthesizes cDNA intracellularly as a late event in the replication cycle. To further confirm this finding, we performed inhibition studies with the reverse transcriptase inhibitor zidovudine (AZT). While AZT had no effect or only a minor effect on virus titers when added to cells prior to virus infection, 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 DNA.

Viral Diseases of Nonhuman Primates

“…Foamy virus reverse transcription occurs during viral assembly or budding such that the process is complete before the virus infects new cells. Subsequently, the functional nucleic acid of SFV consists of double-stranded linear DNA rather than single-stranded RNA (Moebes et al, 1997;Yu et al, 1999). SFV also have two unique nonstructural proteins; Tas is a transcriptional activator, and Bet is involved in latency regulation.…”

Orthoretroviral-like prototype foamy virus gag-pol expression is compatible with viral replication

“…Further details on the cloning procedures and mutagenesis primers used are available upon request. The different PFV proviral Gag-Pol fusion constructs depicted were generated by replacing a 1829 bp SwaI/PacI fragment of the infectious molecular clone pczHSVR2 [38] with the corresponding fragment of eukaryotic constructs expressing only the mutant Gag-Pol fusion proteins. Proviral constructs are labeled with the prefix "P" (e.g.…”

Detection and analysis of bovine foamy virus infection by an indicator cell line

“…Studies indicate that the RT of FV is not at the early phase of infection, but occurs late in the replication cycle before new virus buds from an infected cell. This is held true for both human and feline FV [16][17][18] . However, the step of RT in bovine foamy virus (BFV) has not been defined.…”

“…Using a potent RT inhibitor AZT, Rethwilm and colleagues restricted HFV and FeFV at a late stage of virus infection [17,18] . Similarly, we employed the GFP gene as an indicator to replace the beta-galactosidase gene in the AZT assay, which allowed us to observe viral infection in a living cell system.…”