Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients
Increased expression and dysregulated association of restriction factors and type I interferon in HIV, HCV mono- and co-infected patients
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DOI：
10.1002/jmv.24419
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发表时间：
2016-06-01
影响因子：
12.7
通讯作者：
Zheng, Yong-Tang
中科院分区：
文献类型：
--
作者：
Zhu, Jia-Wu;Liu, Feng-Liang;Zheng, Yong-Tang
宿主限制因子和I型干扰素在限制HIV和丙型肝炎病毒感染中起重要作用，但HIV、丙型肝炎病毒单一感染和混合感染在调节这些抗病毒基因表达方面的作用尚不清楚。本研究检测了43例HIV单一感染者、70例丙型肝炎病毒感染者、感染者和98例健康对照外周血单个核细胞中TRIM5、TRIM22、APOBEC3G和干扰素-α的表达水平。我们还量化了单一感染和混合感染患者中的艾滋病毒和丙型肝炎病毒载量。结果表明，丙型肝炎病毒、艾滋病病毒单独感染和混合感染可显著上调TRIM22、APOBEC3G和干扰素-α的mRNA表达，而TRIM的mRNA表达仅受丙型肝炎病毒单独感染的影响。与艾滋病毒或丙型肝炎病毒单一感染相比，艾滋病毒/丙型肝炎病毒混合感染与更高的病毒载量有关。此外，我们还发现TRIM和TRIM22与干扰素-、-呈正相关，这可能是HIV、丙型肝炎病毒单一感染和联合感染引起的。此外，我们还发现，在单一感染患者中，TRIM22与丙型肝炎病毒载量呈负相关，在合并感染患者中，APOBEC3G与丙型肝炎病毒载量呈正相关。总而言之，我们的发现表明限制因素在限制体内艾滋病毒、丙型肝炎病毒单一感染和联合感染方面的潜在作用，这似乎是潜在药物发现的治疗靶点。J.Med.维罗尔。2016年，88：987-995。(C)2015年威利期刊公司。
Host restriction factors and type I interferon are important in limiting HIV and HCV infections, yet the role of HIV, HCV mono- and co-infection in regulating these antiviral genes expression is not clear. In this study, we measured the levels of TRIM5, TRIM22, APOBEC3G, and IFN-, - mRNA expression in peripheral blood mononuclear cells of 43 HIV mono-infected, 70 HCV mono-infected and 64 HIV/HCV co-infected patients along with 98 healthy controls. We also quantified HIV and HCV viral loads in mono- and co-infected patients. The results showed that HCV, HIV mono- and co-infection differentially increased TRIM22, APOBEC3G, and IFN-, - mRNA expression while the mRNA expression of TRIM was upregulated only by HCV-mono infection. HIV/HCV co-infection was associated with higher viral load, compared to either HIV or HCV mono-infection. Additionally, we showed TRIM and TRIM22 positively correlated with IFN-, -, which could be dysregulated by HIV, HCV mono- and co-infection. Furthermore, we found TRIM22 negatively correlated with HCV viral load in mono-infected patients and APOBEC3G positively correlated with HCV viral load in co-infected patients. Collectively, our findings suggest the potential role of restriction factors in restricting HIV, HCV mono- and co-infection in vivo, which appears to be a therapeutic target for potential drug discovery. J. Med. Virol. 88:987-995, 2016. (c) 2015 Wiley Periodicals, Inc.