Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms.
APOBEC3G (A3G) is an antiretroviral host factor that functions by deaminating dC to dU in retroviral cDNA. HIV-1 Vif protein counteracts A3G via a ubiquitin-proteasome pathway. In the case of a simple retrovirus such as the murine leukemia virus (MLV), it remains unclear why it can replicate in cells expressing APOBEC3 (A3) even though it doesn't possess any accessory proteins such as Vif. In this study, we demonstrate that MLV escapes from murine A3 (mA3) via two distinct novel mechanisms. First, viral RNA (vRNA) blocks the binding of mA3 to Gag, resulting in the exclusion of mA3 from MLV virions. Second, viral protease (vPR) cleaves mA3 after maturation of virions. Here, we suggest that each virus has its own strategy to escape from A3 proteins and that these mechanisms might be used by other viruses that do not possess Vif-like protein. On the other hand, mice possess another form of mA3, delta exon5, that escapes from the cleavage by vPR to show more antiviral activity than the wild type mA3. This also suggests that battles between host intrinsic immunity and viruses have led to the evolution of proteins on both sides.
Abudu
Aierken
A
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
Takaori-Kondo
Akifumi
A
Izumi
Taisuke
T
Shirakawa
Kotaro
K
Kobayashi
Masayuki
M
Sasada
Amane
A
Fukunaga
Keiko
K
Uchiyama
Takashi
T
D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D015683:Gene Products, gag / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D005982:Glutathione Transferase; D006801:Humans; D047468:Immunoprecipitation; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D012367:RNA, Viral / Q000378:metabolism*; D014771:Virion / Q000235:genetics*
D015683:Gene Products, gag; D012367:RNA, Viral; D005982:Glutathione Transferase; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase