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

Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes.
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Zhou X, Liu Z, Zhang J, Adelsberger JW, Yang J, Burton GF,


Zhou X, Liu Z, Zhang J, Adelsberger JW, Yang J, Burton GF, (click to view)

Zhou X, Liu Z, Zhang J, Adelsberger JW, Yang J, Burton GF,

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BMC microbiology 2016 07 2916(1) 172 doi 10.1186/s12866-016-0751-2

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 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.

CONCLUSION
AAT inhibits HIV-1 entry by directly interacting with gp41 through its C-terminus and thereby inhibits HIV-1 infection.

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