Chen Jianbo, Powell Douglas, Hu Wei-Shau
HIV Drug Resistance Program, NCI-Frederick, P.O. Box B, Building 535, Room 336, Frederick, MD 21702, USA.
J Virol. 2006 Oct;80(19):9651-8. doi: 10.1128/JVI.00936-06.
Recent studies indicate that human immunodeficiency virus type 1 (HIV-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. We hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. Alternatively, it is possible that HIV-1 is unique among primate lentiviruses in possessing high recombination rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2 replication have been extensively studied. There are reported differences between the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for RNA packaging in cis and properties of reverse transcriptase and RNase H activities. These biological disparities could lead to differences in recombination rates between the two viruses. Currently, HIV-1 is the only primate lentivirus in which recombination rates have been measured. To test our hypothesis, we established recombination systems to measure the recombination rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus from African green monkeys (SIVagm), in one round of viral replication. We determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are within the same range as the previously measured HIV-1 recombination rates. Taken together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high recombination frequencies; hence, the high recombination potential is most likely a common feature of primate lentivirus replication.
近期研究表明,1型人类免疫缺陷病毒(HIV-1)的重组频率极高,比诸如鼠白血病病毒和脾坏死病毒等简单的γ逆转录病毒高出约1个数量级。我们推测这种高频率的基因重组是灵长类慢病毒的一个共同特征。或者,HIV-1可能是灵长类慢病毒中唯一具有高重组率的病毒。在其他灵长类慢病毒中,仅对HIV-2复制的分子机制进行了广泛研究。据报道,HIV-1和HIV-2的复制机制存在差异,例如对顺式RNA包装的偏好以及逆转录酶和核糖核酸酶H活性的特性。这些生物学差异可能导致两种病毒在重组率上存在差异。目前,HIV-1是唯一已测量重组率的灵长类慢病毒。为了验证我们的假设,我们建立了重组系统,以测量另外两种灵长类慢病毒——HIV-2和来自非洲绿猴的猴免疫缺陷病毒(SIVagm)在一轮病毒复制中的重组率。我们确定,对于间隔588、288和90 bp的标记,HIV-2的重组率分别为7.4%、5.5%和2.4%,而SIVagm的重组率分别为7.8%、5.6%和2.7%。这些高重组率与先前测量的HIV-1重组率处于同一范围。综上所述,我们的结果表明,HIV-1、HIV-2和SIVagm都具有高重组频率;因此,高重组潜力很可能是灵长类慢病毒复制的一个共同特征。