Foamy Viruses, Bet, and APOBEC3 Restriction

Abstract

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

Special Issue “APOBECs and Virus Restriction”

“…Foamy viruses are a unique class of retroviruses and have a unique way of avoiding APOBEC3-mediated suppression, in comparison to HIV [ 17 ]. Vasudevan et al presents literature on foamy virus infection and APOBEC3 restriction [ 17 ].…”

“…Foamy viruses are a unique class of retroviruses and have a unique way of avoiding APOBEC3-mediated suppression, in comparison to HIV [ 17 ]. Vasudevan et al presents literature on foamy virus infection and APOBEC3 restriction [ 17 ]. Evidence suggests that human APOBEC3G, but not simian APOBEC3s, induces mutations, which are lethal to the virus and protect against simian foamy virus transmission [ 17 ].…”

“…Vasudevan et al presents literature on foamy virus infection and APOBEC3 restriction [ 17 ]. Evidence suggests that human APOBEC3G, but not simian APOBEC3s, induces mutations, which are lethal to the virus and protect against simian foamy virus transmission [ 17 ]. Foamy viruses encode a unique protein, Bet, that is highly expressed in infected animals and was demonstrated to sequester APOBEC3s in a degradation-independent manner [ 17 ].…”

“…Evidence suggests that human APOBEC3G, but not simian APOBEC3s, induces mutations, which are lethal to the virus and protect against simian foamy virus transmission [ 17 ]. Foamy viruses encode a unique protein, Bet, that is highly expressed in infected animals and was demonstrated to sequester APOBEC3s in a degradation-independent manner [ 17 ]. This results in an “immobile complex” of the APOBEC3, without triggering degradation of the APOBEC3 [ 17 ].…”

“…Foamy viruses encode a unique protein, Bet, that is highly expressed in infected animals and was demonstrated to sequester APOBEC3s in a degradation-independent manner [ 17 ]. This results in an “immobile complex” of the APOBEC3, without triggering degradation of the APOBEC3 [ 17 ]. This interaction traps the APOBEC3s in the cytoplasm, and thus APOBEC3s are unable to become incorporated into the progeny virions.…”