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.

背景：Talin-1 参与人类免疫缺陷病毒 (HIV) 的入侵和突触发育。我们发现 talin-1 在 HIV 患者的外周血单核细胞 (PBMC) 中被切割成 38 KDa 的片段 (talin-C)；然而，潜在的机制仍然未知。

目的：本研究旨在确定 talin-C 与 HIV 感染之间的关系，并确定该蛋白影响 HIV 感染能力的潜在机制。

方法：PBMC 来自参与本研究的 HIV 感染患者。通过多反应监测 (MRM) 质谱法在 PBMC 中检测到与 talin-C 的潜在序列匹配的 N 和 C 端肽。TZM-b1 细胞用 HIV-1 假型病毒 (HIVpp) 感染不同的持续时间以检测 talin-C 产物。HIVpp 产生并感染了三个过表达 talin 头 (TLN1-H) 或 TLN1-C 或 TLN1 敲低 (shTLN1) 的稳定细胞系。然后通过酶联免疫吸附试验检测 HIV 标记蛋白 (P24)。最后，进行了基于相对和绝对定量 (iTRAQ) 的蛋白质组学研究的同量异位素标记，以检测 TZM-bl 细胞中有或没有 HIVpp 感染的 TLN1-C 调节蛋白。鉴定的蛋白质由 R 4.0 版分析。

结果：检测到talin-C的N-和C-肽在HIV载量较低的患者中具有更高的表达。Talin-C 是在 HIVpp 感染期间产生的。TLN1-C 显着抑制 TZM-b1 细胞中的 HIVpp 感染。此外，蛋白质组学研究发现，TLN1-C 分别调节有和没有 HIVpp 感染的 TZM-b1 细胞中 99 种蛋白质的表达。根据基因本体论（GO）注释，发现具有细胞代谢过程和结合功能的蛋白质被富集。34 个蛋白质具有蛋白质-蛋白质相互作用，分别有 19 个下调和 15 个上调蛋白质。

结论：Talin-C 是在 HIV 感染后产生的，与 HIV 载量成反比。一项蛋白质组学研究表明，TLN1-C 可能通过调节代谢过程参与 HIV 感染。