In vitro characterization of multidrug-resistant HIV-1 isolates from a recently infected patient associated with dual tropism and rapid disease progression.
In vitro characterization of multidrug-resistant HIV-1 isolates from a recently infected patient associated with dual tropism and rapid disease progression.
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DOI：
10.1097/qai.0b013e31817ecb31
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发表时间：
2008-08-15
期刊：
影响因子：
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通讯作者：
Markowitz M
中科院分区：
文献类型：
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作者：
Mohri H;Markowitz M
多药耐药(MDR)-HIV-1变异被认为比野生型病毒更不适合。2005年，我们报告了一例传播性耐多药hiv -1感染，伴有双向性和快速临床进展。在这里，我们报告了病毒分离物的体外特性。对该病例（MDR-1）的散装和克隆分离株的复制特性进行了检测，并与传播的MDR和野生型病毒（MDR-2~4, WT-1, 2）进行了比较。与其他生物克隆（7.3×103TCID50/ml; 1/ 21320）相比，耐多药-1生物克隆（平均滴度3.5×105 TCID50/ml；平均感染病毒频率1/ 2444）及其散装分离物（3.2×106TCID50/ml; 1/301）的传染性和感染病毒频率较高。MDR-1克隆在PBMC培养中病毒复制的上升斜率（log10p24/ml/d）（1.30±0.30:mean±SD）明显高于MDR-2~4克隆（0.75±0.08）或WT-1、-2克隆（0.82±0.03）。与其他测试的病毒相比，从MDR-1中分离的大量分离物和双热带生物克隆在体外非常迅速地耗尽CD4+ T细胞。这些发现支持了多重耐药HIV-1可以有效进化和补偿的假设，不仅保持高水平的复制，而且表现出与疾病快速进展相关的毒力。
Multi-drug resistant (MDR)-HIV-1 variants are thought to be less fit than wild type virus. In 2005 we reported a case of transmitted MDR-HIV-1 infection associated with dual tropism and rapid clinical progression. Here, we report the in vitro characterization of the virus isolates. Replication characteristics of bulk and clonal isolates from this case (MDR-1) were examined and compared with these to a panel of transmitted MDR and wild type viruses (MDR-2~4, WT-1, 2). Infectivity and frequency of infectious virion of propagated isolates were high in MDR-1 biological clones (mean titer, 3.5×105 TCID50/ml; mean frequency of infectious virion, 1/2,444) and its bulk isolate (3.2×106TCID50/ml; 1/301), as compared to the other biological clones (7.3×103TCID50/ml; 1/21,320). Up-slope (log10p24/ml/d) of viral replication in PBMC culture was much higher in MDR-1 clones (1.30±0.30: mean±SD) than those of MDR-2~4 (0.75±0.08) or WT-1, -2 clones (0.82±0.03). The bulk isolate and dual tropic biological clones from MDR-1 depleted CD4+ T cells very rapidly in vitro compared to the other viruses tested. These findings support the hypothesis that multi-drug resistant HIV-1 can effectively evolve and compensate to not only retain high level replication but exhibit virulence associated with rapid disease progression.