Human　APOBEC3G　(hA3G),　a　cytidine　deaminase　with　two　cytidine　deaminase　domains　(CDs),　has　been　identified　as　an　anti-HIV-1　host　factor.　Although　the　two　CDs　of　hA3G　have　been　extensively　characterized,　there　is　still　debate　on　the　role　of　the　CDs　in　the　biological　function　of　hA3G.　In　this　work,　we　constructed　three　hA3G　mutants　CD1-1,　CD2-2　and　CD2-1,　which　contain　duplicate　CD1　domain,　duplicate　CD2　domain　and　position　switched　CD　domain　respectively,　and　investigated　the　effect　of　CD　domain　replacement　or　switch　upon　virion　encapsidation,　Vif-mediated　degradation,　deamination　and　antiviral　activity　of　hA3G.　The　results　showed　that　the　two　CD　domains　were　functionally　equivalent　in　virion　encapsidation　and　the　interaction　with　HIV-1　Vif　of　hA3G,　whereas　CD　domain　switch　or　replacement　greatly　affected　the　sensitivity　to　Vif　induced　degradation,　editing　and　antiviral　activity　of　hA3G.　Although　the　CD2　domain　was　shown　to　possess　the　deamination　activity,　CD2-2　incorporated　efficiently　into　HIV-1　was　unable　to　mutate　viral　cDNA,　suggesting　that　CD1　also　involved　in　the　enzymatic　function.　Interestingly,　CD2-1　retained　considerable　deamination　activity　with　a　different　sequence　preference.　Taken　together,　our　results　suggest　that　CD　domain　may　play　a　structural　role　in　virion　encapsidation　and　Vif-mediated　degradation　of　hA3G,　and　coordination　of　the　two　CD　domains　is　required　for　its　editing　and　antiviral　activity.　(C)　2011　Elsevier　Inc.　All　rights　reserved.