Proteomic Study of the Mechanism of Talin-C as an Inhibitor of HIV Infection

Author(s): Lin Yin, Yujiao Zhang, Huichun Shi, Yaru Xing, Hongzhou Lu, Lijun Zhang*

Journal Name: Current Proteomics

Volume 18 , Issue 5 , 2021


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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.

Keywords: Talin-C, HIV, proteomics, iTRAQ, metabolic pathways, STRING software.

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Article Details

VOLUME: 18
ISSUE: 5
Year: 2021
Published on: 14 December, 2020
Page: [705 - 716]
Pages: 12
DOI: 10.2174/1570164618999201214153239
Price: $25

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