van der Hoek Lia, Pollakis Georgios, Lukashov Vladimir V, Jebbink Maarten F, Jeeninga Rienk E, Bakker Margreet, Dukers Nicole, Jurriaans Suzanne, Paxton William A, Back Nicole K T, Berkhout Ben
Laboratory of Experimental Virology, and Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands.
AIDS Res Hum Retroviruses. 2007 Mar;23(3):466-70. doi: 10.1089/aid.2006.0184.
We identified an HIV-1 variant that belongs to the M group, with limited similarity of short genetic regions (100-200 nt) to subtype K, but the remainder of the genome is unrelated to any established HIV-1 subtype. The isolate was obtained from an HIV-1-positive male, living in the Netherlands, who encountered the virus before 1989, most probably via heterosexual contact in Africa. We describe the full-length genome sequence of four biological clones that were obtained from two samples collected 5 years apart. At both time points all open reading frames were intact. Within the 5-year interval, the person received antiretroviral therapy with zalcitabine and zidovudine for almost 4 years. Evolution of drug-resistant variants is likely given the increase in viral RNA load to +/-10,000 copies/ml during the last year of treatment. Surprisingly, the only regular RT mutation acquired during this period was K70R, which suggests that the genetic background of this variant is perhaps not suitable for the generation of the standard 41L, 67N, and 215Y/F mutations that typically arise during prolonged, nonsuccessful, zidovudine treatment. Awaiting the discovery of at least two additional, epidemiologically unrelated patients with a phylogenetically related HIV-1 variant, we can designate this variant a new HIV-1 subtype, or a distinct branch of subtype K.
我们鉴定出一种属于M组的HIV-1变异株,其短基因区域(100 - 200 nt)与K亚型有有限的相似性,但基因组的其余部分与任何已确定的HIV-1亚型均无关联。该分离株取自一名居住在荷兰的HIV-1阳性男性,他于1989年前感染了该病毒,很可能是在非洲通过异性接触感染的。我们描述了从相隔5年采集的两个样本中获得的四个生物学克隆的全长基因组序列。在两个时间点,所有开放阅读框均完整。在这5年期间,该患者接受了扎西他滨和齐多夫定的抗逆转录病毒治疗近4年。鉴于在治疗的最后一年病毒RNA载量增加到约10,000拷贝/ml,耐药变异株可能发生了进化。令人惊讶的是,在此期间获得的唯一常规RT突变是K70R,这表明该变异株的遗传背景可能不适合产生在长期、未成功的齐多夫定治疗中通常出现的标准41L、67N和215Y/F突变。在等待发现至少另外两名在流行病学上无关联且具有系统发育相关HIV-1变异株的患者之前,我们可以将此变异株指定为一种新的HIV-1亚型,或K亚型的一个独特分支。