Ferns R Bridget, Tarr Alexander W, Hue Stephane, Urbanowicz Richard A, McClure C Patrick, Gilson Richard, Ball Jonathan K, Nastouli Eleni, Garson Jeremy A, Pillay Deenan
Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom; Clinical Microbiology & Virology, UCL Hospital NHS Foundation Trust, United Kingdom.
School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom.
Virology. 2016 May;492:213-24. doi: 10.1016/j.virol.2016.02.003. Epub 2016 Mar 21.
HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.
与单纯丙型肝炎病毒(HCV)感染患者相比,感染人类免疫缺陷病毒1型(HIV-1)后又感染HCV的患者发生慢性化和肝病进展的几率更高。了解这一致病过程中的早期事件很重要。我们应用E1至NS3区域的单基因组测序和病毒假型中和试验,以探究4例合并感染个体(平均随访566天)从血清转化前到慢性化过程中病毒准种进化的后果。我们观察到有1至3种奠基病毒发生了传播。在3例患者中观察到相对较低的病毒序列多样性,这可能与HIV感染导致的免疫反应受损有关。然而,第四例患者在早期纯化选择后,E2序列进化增加,这可能与接受抑制性抗逆转录病毒治疗有关。由HCV变体产生的病毒假型对自体血浆的中和作用表现出相对抗性,但对后期采集的血浆则没有抗性,这证实病毒在持续逃避抗体中和作用。