Markers of Immune Activation and Inflammation Are Associated with Higher Levels of Genetically-Intact HIV in HIV-HBV Co-Infected Individuals.
Markers of Immune Activation and Inflammation Are Associated with Higher Levels of Genetically-Intact HIV in HIV-HBV Co-Infected Individuals.
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DOI：
10.1128/jvi.00588-22
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发表时间：
2022-08-24
影响因子：
5.4
通讯作者：
Palmer, Sarah
中科院分区：
文献类型：
--
作者：
Wang, Xiao Qian;Zerbato, Jennifer M.;Avihingsanon, Anchalee;Fisher, Katie;Schlub, Timothy;Rhodes, Ajantha;Audsley, Jennifer;Singh, Kasha P.;Zhao, Wei;Lewin, Sharon R.;Palmer, Sarah
关键词：
乙肝病毒（HBV）与人类免疫缺陷病毒（HIV）合并感染会增加全因死亡率和肝脏相关死亡率。为了确定这两种病毒在体内的相互作用，研究人员对来自泰国曼谷的HIV - HBV合并感染队列以及HIV单一感染队列的全长HIV前病毒进行了测序，样本采集时间分别为开始抗逆转录病毒治疗（ART）之前以及接受ART至少2年后。研究发现，在治疗前，合并感染个体的基因完整的HIV前病毒水平高于单一感染个体。在这些合并感染个体中，较高水平的基因完整的HIV前病毒或前病毒遗传多样性还与较高水平的可溶性CD14（sCD14）和趋化因子CXCL10相关，这表明免疫激活与更多基因完整的HIV前病毒有关。经过3年的ART治疗，HIV前病毒的总体水平有所下降，在合并感染个体中检测到的基因完整的前病毒数量少于单一感染个体。然而，ART增加了前病毒内某些基因缺陷的发生频率以及相同HIV序列的扩增。
重要意义：随着ART的可及性提高和疗效增强，合并症现已成为HIV阳性个体的主要死因之一。其中一种合并症就是与HBV的合并感染。然而，对于合并感染的研究仍相对不足，尤其是在那些合并感染呈地方性流行的国家。此外，这些国家流行的HIV亚型与常见研究的HIV B亚型不同。我们认为，我们的研究填补了这一研究空白，并为探究HBV合并感染对HIV感染的影响提供了一种新方法。我们从分子层面研究合并感染，以探究这两种病毒通过与免疫系统的相互作用而产生的间接关联。我们证明，HBV合并感染个体中免疫炎症和激活的增加，与更高的HIV病毒血症以及外周血细胞中基因完整的HIV前病毒数量增加有关。这使我们推测，炎症可能是导致HIV - HBV合并感染个体死亡率上升的一个驱动因素。
Co-infection with hepatitis B (HBV) and human immunodeficiency virus (HIV) increases overall and liver-related mortality. In order to identify interactions between these two viruses in vivo, full-length HIV proviruses were sequenced from a cohort of HIV-HBV co-infected participants and from a cohort of HIV mono-infected participants recruited from Bangkok, Thailand, both before the initiation of antiretroviral therapy (ART) and after at least 2 years of ART. The co-infected individuals were found to have higher levels of genetically-intact HIV proviruses than did mono-infected individuals pre-therapy. In these co-infected individuals, higher levels of genetically-intact HIV proviruses or proviral genetic-diversity were also associated with higher levels of sCD14 and CXCL10, suggesting that immune activation is linked to more genetically-intact HIV proviruses. Three years of ART decreased the overall level of HIV proviruses, with fewer genetically-intact proviruses being identified in co-infected versus mono-infected individuals. However, ART increased the frequency of certain genetic defects within proviruses and the expansion of identical HIV sequences. IMPORTANCE With the increased availability and efficacy of ART, co-morbidities are now one of the leading causes of death in HIV-positive individuals. One of these co-morbidities is co-infection with HBV. However, co-infections are still relatively understudied, especially in countries where such co-infections are endemic. Furthermore, these countries have different subtypes of HIV circulating than the commonly studied HIV subtype B. We believe that our study serves this understudied niche and provides a novel approach to investigating the impact of HBV co-infection on HIV infection. We examine co-infection at the molecular level in order to investigate indirect associations between the two viruses through their interactions with the immune system. We demonstrate that increased immune inflammation and activation in HBV co-infected individuals is associated with higher HIV viremia and an increased number of genetically-intact HIV proviruses in peripheral blood cells. This leads us to hypothesize that inflammation could be a driver in the increased mortality rate of HIV-HBV co-infected individuals.
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DOI：
10.1097/qad.0b013e32832e463a
发表时间：
2009-09-10
期刊：
AIDS (London, England)
影响因子：
--
作者：
Hoffmann CJ;Seaberg EC;Young S;Witt MD;D'Acunto K;Phair J;Thio CL
通讯作者：
Thio CL
DOI：
10.1073/pnas.1308313110
发表时间：
2013-12-17
影响因子：
11.1
作者：
Josefsson, Lina;von Stockenstrom, Susanne;Palmer, Sarah
通讯作者：
Palmer, Sarah
影响因子：
168.9
作者：
Maartens, Gary;Celum, Connie;Lewin, Sharon R.
通讯作者：
Lewin, Sharon R.
影响因子：
3.8
作者：
Law, WP;Duncombe, CJ;Dore, GJ
通讯作者：
Dore, GJ
影响因子：
6.4
作者：
Crane, Megan;Avihingsanon, Anchalee;Lewin, Sharon R.
通讯作者：
Lewin, Sharon R.