Significant Reductions in Gag-Protease-Mediated HIV-1 Replication Capacity during the Course of the Epidemic in Japan
Significant Reductions in Gag-Protease-Mediated HIV-1 Replication Capacity during the Course of the Epidemic in Japan
复制标题
日本疫情期间 Gag 蛋白酶介导的 HIV-1 复制能力显着降低
DOI：
10.1128/jvi.02122-12
复制
发表时间：
2013
期刊：
影响因子：
5.4
通讯作者：
and T. Miura.
中科院分区：
文献类型：
--
作者：
Nomura;S.;N. Hosoya;Z. L. Brumme;M. A. Brockman;T. Kikuchi;M. Koga;H. Nakamura;T. Koibuchi;T. Fujii;J. M. Carlson;D. Heckerman;A. Kawana-Tachikawa;A. Iwamoto;and T. Miura.
1 型人类免疫缺陷病毒 (HIV-1) 会因宿主免疫选择压力而迅速进化。因此，流行病早期的 HIV-1 分离株的功能特性可能与流行后期的分离株不同。然而，很少有研究调查疫情期间病毒复制能力（RC）的变化。在本研究中，我们比较了日本早期和晚期分离株（1994 年至 2009 年）的 Gag-Protease 相关 RC。来自 156 名未接受过抗逆转录病毒治疗且患有慢性无症状感染的日本人的 HIV-1 B 亚型序列被用来构建编码血浆来源的 gag 蛋白酶的嵌合 NL4-3 菌株。通过感染长末端重复驱动的绿色荧光蛋白报告T细胞系来检查病毒复制能力。我们观察到嵌合 NL4-3 的 RC 在疫情期间有所下降，在调整 CD4+T 细胞计数和血浆病毒载量后仍然显着。当将分析限制在相关序列的单个大簇时，出现了相同的结果，这表明我们的结果并不是由于日本流行病的分子流行病学的变化所致。此外，RC的变化与患者来源的序列和野生型NL4-3之间的遗传距离无关，从而排除了由于患者和历史病毒主链序列之间的遗传相似性而导致的潜在时间偏差。总的来说，这些数据表明，在日本疫情期间，与 Gag-Protease 相关的 HIV-1 复制能力有所下降。需要对多个地理区域进行更大规模的研究来证实这一现象。
Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in response to host immune selection pressures. As a result, the functional properties of HIV-1 isolates from earlier in the epidemic may differ from those of isolates from later stages. However, few studies have investigated alterations in viral replication capacity (RC) over the epidemic. In the present study, we compare Gag-Protease-associated RC between early and late isolates in Japan (1994 to 2009). HIV-1 subtype B sequences from 156 antiretroviral-naïve Japanese with chronic asymptomatic infection were used to construct a chimeric NL4-3 strain encoding plasma-derivedgag-protease. Viral replication capacity was examined by infecting a long terminal repeat-driven green fluorescent protein-reporter T cell line. We observed a reduction in the RC of chimeric NL4-3 over the epidemic, which remained significant after adjusting for the CD4+T cell count and plasma virus load. The same outcome was seen when limiting the analysis to a single large cluster of related sequences, indicating that our results are not due to shifts in the molecular epidemiology of the epidemic in Japan. Moreover, the change in RC was independent of genetic distance between patient-derived sequences and wild-type NL4-3, thus ruling out potential temporal bias due to genetic similarity between patient and historic viral backbone sequences. Collectively, these data indicate that Gag-Protease-associated HIV-1 replication capacity has decreased over the epidemic in Japan. Larger studies from multiple geographical regions will be required to confirm this phenomenon.