Intrinsic Apoptotic Pathway Genes of Circulating Blood Neutrophils Triggered during HIV Infection and Remained Stimulated in ART Patients.

IF 0.8 4区医学 Q4 IMMUNOLOGY

Current HIV Research Pub Date : 2023-01-01 DOI:10.2174/1570162X21666230519164239

A K M Muraduzzaman, Nabeela Mahboob Islam, Shahina Tabassum, Saif Ullah Munshi

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引用次数: 0

Abstract

Background: The intrinsic apoptotic pathway of neutrophils in Human Immunodeficiency Virus (HIV) infection results in spontaneous neutrophil death. There is a scarcity of data regarding the gene expression of an intrinsic apoptotic pathway of neutrophils in HIV patients.

Objective: The objective of this study was to observe the differential expression of some important genes involved in the intrinsic apoptotic pathway of HIV patients, including those who were receiving antiretroviral therapy (ART).

Methods: Blood samples were collected from asymptomatic, symptomatic, ART receiver HIV patients, and healthy individuals. Total RNA was extracted from neutrophils and subjected to quantitative real-time PCR assay. CD4⁺T cells and an automated complete blood count were performed.

Results: Among the asymptomatic, symptomatic, and ART receiver HIV patients (n=20 in each group), median CD4⁺T counts were 633, 98, and 565 cells/ml, and the length of HIV infection in months (± SD) was 24.06 ± 21.36, 62.05 ± 25.51, and 69.2 ± 39.67, respectively. Compared with healthy controls, intrinsic apoptotic pathway genes, i.e., BAX, BIM, Caspase-3, Caspase-9, MCL-1, and Calpain-1, were upregulated to 1.21 ± 0.33, 1.8 ± 0.25, 1.24 ± 0.46, 1.54 ± 0.21, 1.88 ± 0.30, and 5.85 ± 1.34 fold in the asymptomatic group, and even more significantly, i.e., 1.51 ± 0.43, 2.09 ± 1.13, 1.85 ± 1.22, 1.72 ± 0.85, 2.26 ± 1.34, and 7.88 ± 3.31 fold in symptomatic patients, respectively. Despite CD4⁺ T-cell levels increased in the ART receiver group, these genes did not approach the level of healthy or asymptomatic and remained significantly upregulated.

Conclusion: The genes involved in the intrinsic apoptotic pathway in circulating neutrophils during HIV infection were stimulated in vivo, and ART reduced the expression of those upregulated genes but did not return to the level of asymptomatic or healthy individuals.

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HIV感染期间触发的循环血液中性粒细胞固有凋亡途径基因并在ART患者中保持刺激。

背景:人类免疫缺陷病毒(HIV)感染中中性粒细胞固有的凋亡途径导致中性粒细胞自发性死亡。关于HIV患者中性粒细胞固有凋亡途径的基因表达的数据缺乏。目的:本研究的目的是观察HIV患者(包括接受抗逆转录病毒治疗(ART)的患者)内在凋亡通路中一些重要基因的差异表达。方法:采集无症状感染者、有症状感染者、接受抗逆转录病毒治疗者和健康人群的血液样本。从中性粒细胞中提取总RNA，进行实时荧光定量PCR检测。进行CD4+T细胞和自动全血细胞计数。结果:无症状、有症状、接受ART治疗的HIV患者各20例，CD4+T中位数分别为633、98、565细胞/ml, HIV感染月长(±SD)分别为24.06±21.36、62.05±25.51、69.2±39.67。与健康对照组相比，无症状组固有凋亡通路基因BAX、BIM、Caspase-3、Caspase-9、MCL-1、Calpain-1表达上调至1.21±0.33、1.8±0.25、1.24±0.46、1.54±0.21、1.88±0.30、5.85±1.34倍，有症状组上调幅度更大，分别为1.51±0.43、2.09±1.13、1.85±1.22、1.72±0.85、2.26±1.34、7.88±3.31倍。尽管抗逆转录病毒治疗组CD4+ t细胞水平升高，但这些基因并未接近健康或无症状患者的水平，仍显著上调。结论:体内HIV感染过程中参与循环中性粒细胞内在凋亡通路的基因受到刺激，ART降低了这些上调基因的表达，但没有恢复到无症状或健康个体的水平。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current HIV Research 医学-病毒学

CiteScore

1.90

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.