Study On The Antagonistic Mechanism Of HIV-1 Nef Protein To The Host Restriction Factor SERINC5

SERINC5(Ser5)has 10-12 transmembrane structure,which is host restriction factor has a strong anti HIV-1 virus ability that was first reported in 2015.Different from other host restriction factor has been reported,antiviral ability of SERINC5 can significantly reduce the infectivity of virus release in the late stage of the HIV-1 viral life cycle.The main the mechanism is packaged in virus with the cell membrane,and the greater the amount of the SERINC5 is packed,the stronger the ability to release the virus infection.Many articles reported that HIV-1 virus lack of Nef protein will cause the virus to lose the resistance ability of SERINC5,which due to the virus packing out with SERINC5 protein and then the infection of virus is very low;the content of SERINC5 of virus particles is reduced when the virus containing Nef protein,and then the infection of virus recovery a strong infection.It's indicates that the antagonist mechanism of HIV-1 Nef to SERINC5 is limited SERINC5 antiviral function to a great extent.Therefore,clarifying the interaction mechanism between Nef and SERINC5 is very important for the research of anti HIV-1 drugs with new targets.However,people's understanding of its antagonistic mechanism is only limited to the fact that Nef will change the content of SERINC5 into virus particles.Therefore,this paper is based on previous reports,and I put forward the hypothesis that Nef can affect the protein expression of SERINC5 in cells,and mainly focuses on the antagonistic mechanism of Nef on SERINC5.The following research contents have been carried out: First,to verify the effect of Nef on the antiviral function of SERINC5 and to explore the degradation of SERINC5 protein by Nef on this basis.What is the degradation pathway? And the correlation between the degradation of SERINC and the antiviral function of SERINC5 was further discussed.The res?lts show that: firstly,the package of HIV-1 virus in 293 T cells,and TZMbl cells infected by detection of virus infection,antiviral ability of SERINC5 found in a dose dependent manner.Similarly,we also demonstrate the ability of Nef to antagonize the antiviral function of SERINC5.Secondly,by Western blot,flow cytometry,fluorescence observation and other methods,Nef has the ability of degradation of SERINC5 protein was demonstrated in protein level and cell level,and through the way of drug screening the main effect of Nef on the degradation of SERINC5 is proteasome pathway.Finally,it was proved that inhibition of the degradation pathway of Nef to SERINC5 co?ld increase the antiviral ability of SERINC5.Through these experiments,we found the mechanism of the antagonism of HIV-1 Nef to SERINC5.Moreover,effectively inhibiting the degradation of Nef on SERINC5 will largely enhance the antiviral function of SERINC5,which is very meaningf?l for reducing virus replication and inhibiting the spread of virus.In the future research,we will further explore the degradation mechanism.For example,is Nef also like Vif,VPU and other proteins,which can degrade SERINC5 protein by forming ubiquitin proteasome complex? What are the main components of the ubiquitin proteasome complex formed? These studies will lay the foundation for the design and development of new HIV-1 inhibitors.