Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid.
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.
Derse
David
D
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702-1201, USA. derse@ncifcrf.gov
Hill
Shawn A
SA
Princler
Gerald
G
Lloyd
Patricia
P
Heidecker
Gisela
G
D000071480:APOBEC-3G Deaminase; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003564:Cytidine Deaminase; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism; D016346:Gene Products, vif / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D019251:Nucleocapsid / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D009700:Nucleoside Deaminases / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary / Q000187:drug effects; D012097:Repressor Proteins / Q000494:pharmacology*; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D054320:vif Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D016346:Gene Products, vif; D050505:Mutant Proteins; D010455:Peptides; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase