The glycosylated Gag protein of a murine leukemia virus inhibits the antiretroviral function of APOBEC3.
APOBEC proteins have evolved as innate defenses against retroviral infections. Human immunodeficiency virus (HIV) encodes the Vif protein to evade human APOBEC3G; however, mouse retroviruses do not encode a Vif homologue, and it has not been understood how they evade mouse APOBEC3. We report here a murine leukemia virus (MuLV) that utilizes its glycosylated Gag protein (gGag) to evade APOBEC3. gGag is critical for infection of in vitro cell lines in the presence of APOBEC3. Furthermore, a gGag-deficient virus restricted for replication in wild-type mice replicates efficiently in APOBEC3 knockout mice, implying a novel role of gGag in circumventing the action of APOBEC3 in vivo.
Kolokithas
Angelo
A
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA.
Rosenke
Kyle
K
Malik
Frank
F
Hendrick
Duncan
D
Swanson
Lukas
L
Santiago
Mario L
ML
Portis
John L
JL
Hasenkrug
Kim J
KJ
Evans
Leonard H
LH
D000818:Animals; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015683:Gene Products, gag / Q000737:chemistry / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D007113:Immunity, Innate; D009052:Leukemia Virus, Murine / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000276:immunology
D015683:Gene Products, gag; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase