An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.

Autor:	Guizar P; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada., Abdalla AL; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada., Monette A; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada., Davis K; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada., Caballero RE; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada., Niu M; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada., Liu X; Rady Faculty of Health Science, Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada., Ajibola O; Rady Faculty of Health Science, Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada., Murooka TT; Rady Faculty of Health Science, Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.; Rady Faculty of Health Science, Department of Medical Microbiology and Infectious Disease, University of Manitoba, Winnipeg, MB R3E 0J9, Canada., Liang C; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.; Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada., Mouland AJ; Lady Davis Institute at the Jewish General Hospital, Montréal, QC H3T 1E2, Canada.; Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.; Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 May 27; Vol. 27 (6), pp. 110131. Date of Electronic Publication: 2024 May 27 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110131
Abstrakt:	HIV-1 hijacks host proteins involved in membrane trafficking, endocytosis, and autophagy that are critical for virus replication. Molecular details are lacking but are essential to inform on the development of alternative antiviral strategies. Despite their potential as clinical targets, only a few membrane trafficking proteins have been functionally characterized in HIV-1 replication. To further elucidate roles in HIV-1 replication, we performed a CRISPR-Cas9 screen on 140 membrane trafficking proteins. We identified phosphatidylinositol-binding clathrin assembly protein (PICALM) that influences not only infection dynamics but also CD4 + SupT1 biology. The knockout (KO) of PICALM inhibited viral entry. In CD4 + SupT1 T cells, KO cells exhibited defects in intracellular trafficking and increased abundance of intracellular Gag and significant alterations in autophagy, immune checkpoint PD-1 levels, and differentiation markers. Thus, PICALM modulates a variety of pathways that ultimately affect HIV-1 replication, underscoring the potential of PICALM as a future target to control HIV-1. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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