Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Zhou, Xueyuan; Liu, Zhu; Zhang, Jun; Adelsberger, Joseph; Yang, Jun; Burton, Gregory
• Is Part Of: BMC microbiology. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: HIV-1 -- Alpha-1-antitrypsin -- Reverse transcriptase -- Integrase -- gp41; Microbiology -- Periodicals; 579.05
• DOI: 10.1186/s12866-016-0751-2
• Languages: English
• ISSNs: 1471-2180

Abstract

Abstract Background Study 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. Results In 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 detectcis -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. Conclusion AAT inhibits HIV-1 entry by directly interacting with gp41 through its C-terminus and thereby inhibits HIV-1 infection.