Instituto de Investigaciones Biomédicas en Retrovirus y Sida, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Antiviral Res. 2012 Aug;95(2):72-81. doi: 10.1016/j.antiviral.2012.05.015. Epub 2012 Jun 7.
The rate of non-response to pegylated interferon plus ribavirin (peg-IFN+RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism.
We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN+RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN+RBV non-responders and infected with HCV 1a.
Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean±SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80±0.77 vs. 0.95±1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47±1.13 vs. 1.60±1.57; p=0.06). No differences were found at the E2-PePHD (0±0 vs. 0.2±0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24h, 4weeks, and 12weeks).
Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN+RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.
与 HCV 单感染患者相比，HCV/HIV 合并感染患者对聚乙二醇干扰素联合利巴韦林（peg-IFN+RBV）的无应答率更高。在这种情况下，HCV 遗传变异性的作用尚不清楚。5'非翻译区（5'UTR）、非结构 5A（NS5A）和第二包膜（E2）HCV 基因组区域与 peg-IFN 治疗反应有关。这些蛋白似乎可以阻断干扰素（IFN）诱导的 RNA 依赖性蛋白激酶（PKR），而 5'UTR 可能影响病毒的淋巴亲嗜性。
我们比较了 HIV 合并感染和 HCV 单感染患者治疗前 HCV 变异性，并评估了 HIV 共存在时 peg-IFN+RBV 对 HCV 变异性的影响。为此，我们比较了 15 名 HIV 合并感染和 20 名 HCV 单感染的患者。他们都是 peg-IFN+RBV 无应答者，感染的是 HCV 1a。
无论 HIV 共存与否，在基线时，NS5A 相关区域的氨基酸变异显著高于 E2-PePHD（p<0.001）。与 HCV 单感染患者相比，HCV/HIV 患者的 NS5A-ISDR 域的氨基酸变异数（平均值±标准差）更高（1.80±0.77 比 0.95±1.05；p=0.009），但在比较 NS5A-PKRBD 序列时，这种差异略低（2.47±1.13 比 1.60±1.57；p=0.06）。E2-PePHD 无差异（0±0 比 0.2±0.4）。在 HIV 合并感染患者个体水平上，治疗期间仅观察到较小的（HCV 基因分析）或无（HCV 替换率和准种异质性）变化（基础、24 小时、4 周和 12 周）。
在 HCV-1a/HIV 合并感染和 HCV 单感染 peg-IFN+RBV 无应答患者中，5'UTR、E2-PePHD 和 NS5A-PKRBD/ISDR 区域的 HCV 变异性大多相似，变异数较少。当 HIV 共存时，NS5A-ISDR 域中出现了四个明确的氨基酸取代，最为常见。基于干扰素的治疗并未对上述 HCV 区域的变异、选择或多样性产生任何影响，这些区域可能会影响 IFN 治疗的临床反应性。
