Lamers Susanna L, Salemi Marco, Galligan Derek C, de Oliveira Tulio, Fogel Gary B, Granier Sara C, Zhao Li, Brown Joseph N, Morris Alanna, Masliah Eliezer, McGrath Michael S
BioInfoExperts, Thibodaux, LA, USA.
PLoS One. 2009;4(3):e5065. doi: 10.1371/journal.pone.0005065. Epub 2009 Mar 31.
There is evidence that immune-activated macrophages infected with the Human Immunodeficiency Virus (HIV) are associated with tissue damage and serve as a long-lived viral reservoir during therapy. In this study, we analyzed 780 HIV genetic sequences generated from 53 tissues displaying normal and abnormal histopathology. We found up to 50% of the sequences from abnormal lymphoid and macrophage rich non-lymphoid tissues were intra-host viral recombinants. The presence of extensive recombination, especially in non-lymphoid tissues, implies that HIV-1 infected macrophages may significantly contribute to the generation of elusive viral genotypes in vivo. Because recombination has been implicated in immune evasion, the acquisition of drug-resistance mutations, and alterations of viral co-receptor usage, any attempt towards the successful eradication of HIV-1 requires therapeutic approaches targeting tissue macrophages.
有证据表明,感染人类免疫缺陷病毒(HIV)的免疫激活巨噬细胞与组织损伤有关,并在治疗期间作为一个长期的病毒储存库。在本研究中,我们分析了从53个显示正常和异常组织病理学的组织中产生的780个HIV基因序列。我们发现,来自异常淋巴组织和富含巨噬细胞的非淋巴组织的序列中,高达50%是宿主内病毒重组体。广泛重组的存在,特别是在非淋巴组织中,意味着HIV-1感染的巨噬细胞可能在体内显著促成难以捉摸的病毒基因型的产生。由于重组与免疫逃避、耐药性突变的获得以及病毒共受体使用的改变有关,任何成功根除HIV-1的尝试都需要针对组织巨噬细胞的治疗方法。