Cornelissen Marion, Hoogland Frederik M, Back Nicole K T, Jurriaans Suzanne, Zorgdrager Fokla, Bakker Margreet, Brinkman Kees, Prins Maria, van der Kuyl Antoinette C
Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam, The Netherlands.
AIDS. 2009 Jul 31;23(12):1495-500. doi: 10.1097/QAD.0b013e32832d9267.
The evolution of HIV-1 is largely shaped by the cytotoxic T-cell (CTL) response of the host as encoded by the human leucocyte antigen (HLA) genes. Certain HLA-B alleles can delay disease progression, but it is uncertain whether this protection will sustain or whether the virus is in the process of adaptation. In The Netherlands, HLA-B27 is moderately prevalent (approximately 8-16% of HLA-B alleles). If adaptation to HLA-B alleles is in progress, virus strains carrying escape mutations to HLA-B27 should appear in the epidemic by now.
A subtype B HIV-1 strain carrying a HLA-B27 CTL-escape mutation in the main Gag-p24 KK10 epitope, R264G, together with a compensatory mutation outside this epitope, E260D, was detected in four patients from Amsterdam, The Netherlands, by sequence analysis of the gag gene. The patients were a drug user and three men who have sex with men, and were infected with HIV-1 between 2002 and 2008.
Characterization and evolutionary analysis of the HIV-1 CTL-escape strain was done by sequence analysis of serial blood plasma samples.
The mutations involved were stable during follow-up and after transmission, also in two individuals lacking HLA-B27.
The finding that a stable HLA-B27 CTL-escape strain is circulating in The Netherlands has important implications for the understanding of virus-host interactions and vaccine design alike. Vaccines targeted at inducing a CTL response might easily be circumvented by the virus. Also, patients carrying protective HLA alleles might not be protected anymore from disease progression in the future.
人类免疫缺陷病毒1型（HIV-1）的进化很大程度上受宿主细胞毒性T细胞（CTL）反应的影响，该反应由人类白细胞抗原（HLA）基因编码。某些HLA-B等位基因可延缓疾病进展，但尚不确定这种保护作用是否会持续，以及病毒是否正处于适应过程中。在荷兰，HLA-B27的流行程度中等（约占HLA-B等位基因的8%-16%）。如果病毒正在适应HLA-B等位基因，那么目前流行的病毒株中应该会出现对HLA-B27产生逃逸突变的毒株。
通过对gag基因进行序列分析，在荷兰阿姆斯特丹的4名患者中检测到一种B亚型HIV-1毒株，该毒株在主要的Gag-p24 KK10表位R264G处携带HLA-B27 CTL逃逸突变，并在该表位外携带一个补偿性突变E260D。这4名患者包括一名吸毒者和三名男同性恋者，他们于2002年至2008年期间感染了HIV-1。
通过对系列血浆样本进行序列分析，对该HIV-1 CTL逃逸毒株进行特征描述和进化分析。
所涉及的突变在随访期间以及传播后都是稳定的，在两名不携带HLA-B27的个体中也是如此。
在荷兰发现一种稳定的HLA-B27 CTL逃逸毒株，这对于理解病毒与宿主的相互作用以及疫苗设计都具有重要意义。旨在诱导CTL反应的疫苗可能很容易被病毒规避。此外，携带保护性HLA等位基因的患者未来可能无法再免受疾病进展的影响。
