Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Front Immunol. 2023 Feb 9;14:1123600. doi: 10.3389/fimmu.2023.1123600. eCollection 2023.
Heat shock protein (HSPs) are important intracellular factors, which are often involved in the regulation of viral replication including HIV-1 in infected individuals as molecular chaperone proteins. Heat shock proteins 70 (HSP70/HSPA) family play important roles in HIV replication, but this family contain many subtypes, and it is unclear how these subtypes participate in and affect HIV replication.
To detect the interaction between HSPA14 and HspBP1 by CO-IP. Simulating HIV infection status to detect the change of intracellular HSPA14 expression after HIV infection in different cells. Constructing HSPA14 overexpression or knockdown cells to detect intracellular HIV replication levels after infection. Detecting the difference of HSPA expression levels in CD4+ T cells of untreated acute HIV-infected patients with different viral load.
In this study, we found that HIV infection can lead to changes in the transcriptional level of many HSPA subtypes, among which HSPA14 interacts with HIV transcriptional inhibitor HspBP1. The expression of HSPA14 in Jurkat and primary CD4+T cells infected with HIV were inhibited, overexpression of HSPA14 inhibited HIV replication, while knocking down HSPA14 promoted HIV replication. We also found that the expression level of HSPA14 is higher in peripheral blood CD4+T cells of untreated acute HIV infection patients with low viral load.
HSPA14 is a potential HIV replication inhibitor and may restrict HIV replication by regulating the transcriptional inhibitor HspBP1. Further studies are needed to determine the specific mechanism by which HSPA14 regulates viral replication.
热休克蛋白（HSPs）是重要的细胞内因子，它们通常作为分子伴侣蛋白参与包括 HIV-1 在内的病毒复制的调节。热休克蛋白 70（HSP70/HSPA）家族在 HIV 复制中发挥重要作用，但该家族包含许多亚型，目前尚不清楚这些亚型如何参与和影响 HIV 复制。
通过 CO-IP 检测 HSPA14 和 HspBP1 之间的相互作用。模拟 HIV 感染状态，检测 HIV 感染后不同细胞内 HSPA14 表达的变化。构建 HSPA14 过表达或敲低细胞，检测感染后细胞内 HIV 复制水平。检测未经治疗的急性 HIV 感染患者中不同病毒载量的 CD4+T 细胞中 HSPA 表达水平的差异。
本研究发现，HIV 感染可导致许多 HSPA 亚型的转录水平发生变化，其中 HSPA14 与 HIV 转录抑制剂 HspBP1 相互作用。HIV 感染 Jurkat 和原代 CD4+T 细胞后 HSPA14 的表达受到抑制，过表达 HSPA14 抑制 HIV 复制，而敲低 HSPA14 则促进 HIV 复制。我们还发现，未经治疗的急性 HIV 感染患者外周血 CD4+T 细胞中低病毒载量的 HSPA14 表达水平较高。
HSPA14 是一种潜在的 HIV 复制抑制剂，可能通过调节转录抑制剂 HspBP1 来限制 HIV 复制。需要进一步研究确定 HSPA14 调节病毒复制的具体机制。
