Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.
Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.
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DOI：
10.1016/j.virol.2016.02.003
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发表时间：
2016-05
期刊：
影响因子：
3.7
通讯作者：
R. B. Ferns;A. Tarr;S. Hué;R. Urbanowicz;C. P. McClure;R. Gilson;J. Ball;E. Nastouli;J. Garson;D. Pillay
中科院分区：
文献类型：
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作者：
R. B. Ferns;A. Tarr;S. Hué;R. Urbanowicz;C. P. McClure;R. Gilson;J. Ball;E. Nastouli;J. Garson;D. Pillay
获得HCV感染的HIV-1感染患者的慢性化和肝病进展率高于HCV单一感染患者。了解这种致病过程的早期事件是重要的。我们应用E1至NS 3区域的单基因组测序和病毒假型中和试验来探索4个共感染个体中病毒准种从血清转化前向慢性演变的后果（平均随访566天）。我们观察到有一到三种创始病毒被传播。相对较低的病毒序列多样性，可能与受损的免疫反应，由于艾滋病毒感染，在3例患者中观察到。然而，第四例患者，经过早期纯化选择显示E2序列进化增加，可能与抑制性抗逆转录病毒治疗有关。从HCV变体产生的病毒假型显示出对自体血浆中和的相对抗性，但对从稍后时间点收集的血浆没有抗性，证实了正在进行的病毒逃避抗体中和。
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.