Penton Patricia K, Blackard Jason T
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio.
AIDS Res Hum Retroviruses. 2014 Apr;30(4):394-402. doi: 10.1089/AID.2013.0146. Epub 2013 Oct 25.
Liver disease is now a major cause of morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). An increasing body of evidence suggests that HIV infection is associated with exacerbated liver fibrosis and that HIV has the ability to infect several hepatic cell types. Despite the recognized existence of genetically distinct subpopulations of HIV in the central nervous system and genital tract, viral diversity and compartmentalization in the liver have not been explored extensively. Therefore, phylogenetic analysis was performed on full-length env and nef sequences for four patients. Distinct clustering of viral variants was observed for all patients in both areas of the genome. Statistical evidence of HIV compartmentalization in the liver was demonstrated in 85.4% of comparisons. Signature sequence analysis identified several liver-specific amino acids in all patients. Thus, the current study demonstrates statistically significant evidence for HIV compartmentalization in the liver. Additionally, these data suggest that the hepatic microenvironment harbors unique selective pressures that drive viral adaptation.
肝病现已成为感染人类免疫缺陷病毒(HIV)人群发病和死亡的主要原因。越来越多的证据表明,HIV感染与肝纤维化加剧有关,且HIV能够感染多种肝细胞类型。尽管人们已经认识到HIV在中枢神经系统和生殖道中存在基因不同的亚群,但肝脏中的病毒多样性和区室化尚未得到广泛研究。因此,对4例患者的全长env和nef序列进行了系统发育分析。在基因组的这两个区域,所有患者均观察到病毒变体的明显聚类。在85.4%的比较中证明了肝脏中HIV区室化的统计学证据。特征序列分析在所有患者中鉴定出几种肝脏特异性氨基酸。因此,当前研究证明了肝脏中HIV区室化具有统计学意义的证据。此外,这些数据表明肝脏微环境具有驱动病毒适应性的独特选择压力。