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APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz

机译:在启动包含头孢立韦或依非韦伦的抗逆转录病毒疗法后在人类免疫缺陷病毒1型感染个体中APOBEC3G / 3A表达

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摘要

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4+ cell count and CD4+/CD8+ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies.
机译:载脂蛋白B mRNA编辑酶催化多肽样3(APOBEC3)家庭成员是胞苷脱氨酶,在逆转录病毒感染的先天反应中起关键作用。这些酶中的某些限制人免疫缺陷病毒1型(HIV-1)复制的机制已在体外进行了广泛研究。但是,关于APOBEC3蛋白如何影响体内HIV-1感染的发病机理以及抗逆转录病毒疗法如何影响其表达的了解甚少。在这项工作中,我们进行了纵向分析,以评估在基线,4、12、24,以及治疗后48周的随访。虽然APOBEC3G的表达不受治疗影响,但在治疗的第48周,CVC中APOBEC3A的水平升高,而EFV组则没有。 APOBEC3G表达与CD4 + 细胞计数和CD4 + / CD8 + 细胞比率直接相关,而APOBEC3A水平与血浆可溶性CD14呈负相关。这些发现表明,较高的APOBEC3G / 3A水平可能与针对HIV-1疾病进展和慢性炎症的保护作用有关,值得进一步研究。

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