Urokinase plasminogen activator surface receptor restricts HIV-1 replication by blocking virion release from the cell membrane.
Proc Natl Acad Sci U S A
; 120(3): e2212991120, 2023 01 17.
Article
em En
| MEDLINE
| ID: mdl-36638209
ABSTRACT
The urokinase-type plasminogen activator (uPA) system consists of the proteinase uPA, its receptor (PLAUR/uPAR). Under physiological conditions, uPA and PLAUR are predominantly expressed by blood cells, including neutrophils, monocytes, and macrophages, and play important roles in cell activation, adhesion, migration, and extravasation. Here, we report that PLAUR, which is highly expressed in macrophages and dendritic cells (DCs) but hardly expressed in CD4+ T cells, inhibits the release of HIV-1 progeny virions from the cell membrane. Silencing PLAUR markedly enhanced the transmission of HIV-1 in macrophages and DCs. We further demonstrated that PLAUR is localized at the cell membrane to block the release of HIV-1 virions. Interestingly, we found that uPA compromises the PLAUR-mediated inhibition to slightly enhance HIV-1 production in primary macrophages and DCs. In the absence of PLAUR, this enhanced effect induced by uPA is abrogated. In conclusion, PLAUR is a new anti-HIV-1 protein produced in both macrophages and DCs where it inhibits HIV-1 transmission. This discovery may provide a novel therapeutic target for combating HIV.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
HIV-1
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Receptores de Ativador de Plasminogênio Tipo Uroquinase
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article