Roles Of SERINC Family In HIV-1 Infectivity

Serine incorporater（Ser）is a unique membrane protein family.Ser5,a member of the Ser family,has been reported to be a novel host restriction factor that can be incorporated into HIV-1 virion and inhibits viral replication at the step of viral entry.The effect of Ser5 can be counteracted by viral Nef proein.However,the expression status of endogenous Ser5 in host cells and the molecular mechanism of Ser5antiviral activity are still not clear.Here we confirmed that,among five members of Ser,only Ser5 is able to significantly inhibit the infectivity of HIV-1 virion.We found that Ser5 produces 5 alternatively spliced isoforms:Ser5-001 has 10 putative transmembrane domains,whereas Ser5-004,-005,-008a,and-008b lack the last one.We furthur found that Ser5-001 transcripts are expressed at the least 10-fold more than the other isoforms by real-time quantitative PCR.To map the determinant,Ser5 mutants bearing C-terminal deletions were created.Compared with the wild type Ser5-001,the mutants that do not have the 10^th transmembrane domain show a very poor antiviral activity,indicating the 10^th transmembrane domain is required for antiviral activity of Ser5.Interstingly,the expression vector that harbors CMV promoter leads remarkble high expression of Ser5,that viral Nef protein can not conteract Ser5 activity.Using an alternative vector that CMV promoter was replaced with relatively weak SV40promoter,we found that Nef can overcome the activity of Ser5-001 in a dose dependent manner.This study provides a reference for further understanding of the molecular mechanism of antiviral activity of Ser5.Our results also indicate that Ser5-001 can be used as a novel anti-HIV-1 virus molecule in the development of novel antiviral therapy and drugs or other aspects of application prospects.