Abstract
Foamy viruses (FVs) are nonpathogenic retroviruses infecting many species of mammals, notably primates, cattle, and cats. We have examined whether members of the apolipoprotein B-editing catalytic polypeptide-like subunit (APOBEC) family of antiviral cytidine deaminases restrict replication of simian FV. We show that human APOBEC3G is a potent inhibitor of FV infectivity in cell culture experiments. This antiviral activity is associated with cytidine editing of the viral genome. Both molecular FV clones and primary uncloned viruses were susceptible to APOBEC3G, and viral infectivity was also inhibited by murine and simian APOBEC3G homologues, as well as by human APOBEC3F. Wild-type and bet-deleted viruses were similarly sensitive to this antiviral activity, suggesting that Bet does not significantly counteract APOBEC proteins. Moreover, we did not detect FV sequences that may have been targeted by APOBEC in naturally infected macaques, but we observed a few G-to-A substitutions in humans that have been accidentally contaminated by simian FV. In infected hosts, the persistence strategy employed by FV might be based on low levels of replication, as well as avoidance of cells expressing large amounts of active cytidine deaminases.
Highlights
Foamy viruses (FVs) are nonpathogenic retroviruses infecting many species of mammals, notably primates, cattle, and cats
The virus was very sensitive to this inhibitory effect, which was observed at low molar ratios of hA3G:FV expression plasmids (Fig. 1B)
In the absence of hA3G, a small decrease of viral infectivity was detected with ⌬bet, compared to FV, as previously reported (Fig. 1C) [74]. hA3G efficiently inhibited ⌬bet, and a similar antiviral activity was observed against both viruses in a dose-response analysis of hA3G expression level (Fig. 1C)
Summary
Foamy viruses (FVs) are nonpathogenic retroviruses infecting many species of mammals, notably primates, cattle, and cats. We show that human APOBEC3G is a potent inhibitor of FV infectivity in cell culture experiments This antiviral activity is associated with cytidine editing of the viral genome. Foamy viruses (FVs) or spumaretroviruses represent a large family of retroviruses that have been isolated in various mammals (for recent reviews, see references 11, 15, and 35) They are highly prevalent in nonhuman primates, and at least 11 different simian FV (SFV) viral subtypes have been described in monkey species [7, 15, 44]. It was initially reported that CD8ϩ T cells may represent a viral reservoir in monkeys (African green monkeys [AGM] and chimpanzees) and in some humans [66] This tropism for CD8ϩ cells was not observed in another study of a patient infected by AGM FV, which detected FV in monocytes and B cells and not in CD8 lymphocytes [8].
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