Tirado Grissell, Jove Gloria, Kumar Rakesh, Noel Richard J, Reyes Evelyn, Sepulveda Gladys, Yamamura Yasuhiro, Kumar Anil
Laboratory of Viral Immunology, Ponce School of Medicine, PuertoRico 00732.
AIDS Res Hum Retroviruses. 2004 Jun;20(6):684-6. doi: 10.1089/0889222041217509.
Development of a drug-resistant variant of HIV-1 has been one of the major concerns contributing to the transmission of the virus. A 40-year-old woman presented to the clinic with micosis and oral candidiasis. The subject was referred for HIV-1 diagnosis. Subsequent investigations revealed a very low CD4 T cell count (48 cell/microl blood) and high plasma HIV-1 RNA load (4.33 x 10(5) copy/ml). A 1.3-kb pol fragment was sequenced in virus collected from plasma and the vaginal compartment. Plasma virus had no mutation in reverse transcriptase and one mutation in protease (L63P). On the other hand vaginal virus contained L63P and M184V mutations in protease and reverse transcriptase, respectively. These mutations were accompanied by several other mutations in previously identified CTL epitopic regions of the two genes. In the absence of antiretroviral treatment, a drug-resistant mutant was thought to develop because of immune pressure. This is the first report describing the role of immune pressure in the development of a drug-resistant virus.
HIV-1耐药变异体的出现一直是该病毒传播的主要担忧之一。一名40岁女性因霉菌病和口腔念珠菌病到诊所就诊。该患者被转诊进行HIV-1诊断。随后的调查显示其CD4 T细胞计数极低(每微升血液48个细胞),血浆HIV-1 RNA载量很高(4.33×10⁵拷贝/毫升)。对从血浆和阴道腔采集的病毒中的一个1.3千碱基的pol片段进行了测序。血浆病毒的逆转录酶没有突变,蛋白酶有一个突变(L63P)。另一方面,阴道病毒的蛋白酶和逆转录酶分别含有L63P和M184V突变。这些突变伴随着这两个基因先前确定的CTL表位区域中的其他几个突变。在没有抗逆转录病毒治疗的情况下,由于免疫压力,被认为产生了耐药突变体。这是第一份描述免疫压力在耐药病毒产生中作用的报告。