Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4 T lymphocytesReport as inadecuate




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BMC Microbiology

, 16:172

Microbe-host interactions and microbial pathogenicity

Abstract

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 steps 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.

KeywordsHIV-1 Alpha-1-antitrypsin Reverse transcriptase Integrase gp41 Electronic supplementary materialThe online version of this article doi:10.1186-s12866-016-0751-2 contains supplementary material, which is available to authorized users.

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Author: Xueyuan Zhou - Zhu Liu - Jun Zhang - Joseph W. Adelsberger - Jun Yang - Gregory F. Burton

Source: https://link.springer.com/



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