Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

Abstract

Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes in vivo, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing an accessory protein, Vif, which hastens the degradation of hA3G. In contrast, HTLV-1 does not encode a Vif homologue; instead, HTLV-1 has evolved a cis-acting mechanism to prevent hA3G restriction. We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction. Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins.

Murine leukemia virus glycosylated Gag blocks apolipoprotein B editing complex 3 and cytosolic sensor access to the reverse transcription complex

“…Some retroviruses, such as HIV, simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV), encode Vif proteins that bind APOBEC3 proteins and target them for degradation in virus-producing cells. Additionally, the Bet protein of feline foamy viruses inhibits APOBEC3 by as yet undetermined means (16) and human T-cell leukemia virus I prevents packaging of APOBEC3G, although not APOBEC3A, 3B, or 3H (47,48). However, APOBEC3 inhibits infection by a number of viruses that encode no apparent vif-or bet-like genes, and how these viruses overcome restriction is not known.…”

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax

“…However, restriction factors for HTLV-1 have not been studied extensively. It has been reported that APO-BEC3G suppresses replication of HTLV-1 whereas Gag protein inhibits incorporation of APOBEC3G into the virion (32). Recently, SAMHD1 has been reported to suppress replication of HTLV-1 in monocytes (33).…”

APOBEC proteins and intrinsic resistance to HIV-1 infection

“…More straightforward alternatives might be to avert APOBEC proteins by not encapsidating them into virions (e.g. human T-cell leukaemia virus type-I, HTLV-I, and Mason-Pfizer monkey virus, M-PMV ) (Doehle et al 2006;Derse et al 2007) or, perhaps, by simply replicating in nonexpressing cells (Delebecque et al 2006).…”