Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes

BMC Microbiology

Research Article

Jun Yang¹  Xueyuan Zhou¹  Joseph W. Adelsberger¹  Gregory F. Burton²  Jun Zhang³  Zhu Liu⁴ 

[1] Clinic Services Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 21702, Frederick, MD, USA;Department of Chemistry and Biochemistry, Brigham Young University, 84602, Provo, UT, USA;Department of Chemistry, University of Alabama at Birmingham, 35294, Birmingham, AL, USA;Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Agriculture, Hainan University, 570228, Haikou, Hainan, China;

关键词: HIV-1;    Alpha-1-antitrypsin;    Reverse transcriptase;    Integrase;    gp41;   

DOI  :  10.1186/s12866-016-0751-2

 received in 2016-01-11, accepted in 2016-06-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundStudy of a clinic case reveals that alpha-1-antitrypsin (AAT) deficiency is related to CD4+ T cell count decline and AIDS progression, suggesting that AAT might be an endogenous inhibitor of HIV/AIDS. Previous study shows that AAT inhibits HIV-1 replication in infected host cells and the C-terminus fragment of AAT, VIRIP, interferes with HIV-1 infection. However, it is still unclear whether and how intact AAT inhibits HIV-1 infection. It is also unknown what the mechanism of AAT is and which critical step(s) are involved.ResultsIn the present study, the C-terminus of AAT (C) was synthesized. C terminus-truncated AAT (ΔAAT) was also prepared by digesting AAT with metalloproteinase. Primary CD4+ T cells were then co-cultured with HIV-1 with the presence or absence of AAT/C/ΔAAT to detect cis-infection of HIV-1. The interaction between AAT/C/ΔAAT and gp120/gp41 was also measured. Meanwhile, HIV-1 reverse transcriptase activity and viral DNA integration were also detected in these lymphocytes. The results demonstrated that AAT and C, not ΔAAT, inhibited HIV-1 entry by directly interacting with gp41. Meanwhile, AAT, C and ΔAAT could not directly interfere with the steps of viral RNA reverse transcription and viral DNA integration.ConclusionAAT inhibits HIV-1 entry by directly interacting with gp41 through its C-terminus and thereby inhibits HIV-1 infection.

【 授权许可】

CC BY   
© The Author(s). 2016