Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4+ T cells by degrading viral Gag polyprotein.

Abstract:

:Resting CD4+ T cells are highly resistant to the production of human immunodeficiency virus type 1 (HIV-1). However, the mechanism by which resting CD4+ T cells restrict such production in the late viral replication phase of infection has remained unclear. In this study, we found that the cell membrane metalloprotease TRAB domain-containing protein 2A (TRABD2A) inhibited this production in resting CD4+ T cells by degrading the virion structural precursor polyprotein Gag at the plasma membrane. Depletion or inhibition of metalloprotease activity by TRABD2A profoundly enhanced HIV-1 production in resting CD4+ T cells. TRABD2A expression was much higher in resting CD4+ T cells than in activated CD4+ T cells and was considerably reduced by T cell activation. Moreover, reexpressing TRABD2A reinforced the resistance of activated CD4+ T cells to the production of HIV-1 progeny. Collectively, these results elucidate the molecular mechanism employed by resting CD4+ T cells to potently restrict the assembly and production of HIV-1 progeny.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Liang G,Zhao L,Qiao Y,Geng W,Zhang X,Liu M,Dong J,Ding H,Sun H,Shang H

doi

10.1038/s41590-019-0385-2

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

711-723

issue

6

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-019-0385-2

journal_volume

20

pub_type

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