Proteomic Study of the Mechanism of Talin-C as an Inhibitor of HIV Infection
Author:
Yin Lin1,
Zhang Yujiao1,
Shi Huichun1,
Xing Yaru1,
Lu Hongzhou1,
Zhang Lijun1ORCID
Affiliation:
1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Abstract
Background:
Talin-1 is involved in the invasion and synapse development of the Human
Immunodeficiency Virus (HIV). We found that talin-1 was cleaved into a 38 KDa fragment
(talin-C) in the Peripheral Blood Mononuclear Cells (PBMCs) of HIV patients; however, the underlying
mechanisms remain unknown.
Objective:
This study aimed to determine the relationship between talin-C and HIV infection and
to identify the mechanisms underlying the ability of this protein to influence HIV infection.
Methods:
PBMCs were derived from HIV-infected patients enrolled in this study. N- and C-terminal
peptides matching the potential sequence of talin-C were detected in PBMCs by Multiple Reaction
Monitoring (MRM) mass spectrometry. TZM-b1 cells were infected with HIV-1 pseudotyped
virus (HIVpp) for different durations to detect the talin-C product. Three stable cell lines overexpressing
the talin head (TLN1-H) or TLN1-C or with TLN1 knockdown (shTLN1) were created and
infected by HIVpp. The HIV marker protein (P24) was then detected by enzyme-linked immunosorbent
assay. Finally, an isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics
study was performed to detect the TLN1-C-regulated proteins with or without HIVpp infection
in TZM-bl cells. The identified proteins were analyzed by R version 4.0.2 and STRING software
(Version: 11.0) (https://string-db.org).
Results:
N- and C-peptides of talin-C were detected to have higher expression in patients with lower
HIV load. Talin-C was produced during HIVpp infection. TLN1-C significantly inhibited HIVpp
infection in the TZM-b1 cells. Additionally, a proteomic study found that TLN1-C regulated the expression
of 99 proteins in TZM-b1 cells with and without HIVpp infection, respectively. According
to Gene Ontology (GO) annotation, proteins with cellular metabolic processes and binding function
were found to be enriched. Thirty-four proteins have protein-protein interaction, 19 down- and
15 up-regulated proteins, respectively.
Conclusion:
Talin-C was produced following HIV infection and was inversely proportional to
HIV load. A proteomic study indicated that TLN1-C might be involved in HIV infection through
regulating metabolic processes.
Funder
Key Issues of Shanghai Municipal Commission of Health and Family Planning
13th Five-Year New Drug Platform, China
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Molecular Biology,Biochemistry