Kanari Yasuyoshi, Clerici Mario, Abe Hiroyuki, Kawabata Hiroyuki, Trabattoni Daria, Caputo Sergio Lo, Mazzotta Francesco, Fujisawa Hironori, Niwa Atsuko, Ishihara Chiaki, Takei Yumiko A, Miyazawa Masaaki
Department of Immunology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
AIDS. 2005 Jul 1;19(10):1015-24. doi: 10.1097/01.aids.0000174447.48003.dd.
Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene.
Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure.
A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups.
The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.
尽管多次反复接触HIV-1,但一些个体未检测到HIV基因组,且对病毒抗原表现出T细胞记忆反应。在此类未感染个体中检测到的HIV-1反应性黏膜IgA提示他们可能对HIV具有免疫抵抗力。我们测试了上述暴露于HIV-1但未感染的状态是否与除CCR5基因纯合缺失以外的遗传标记有关。
基于我们在小鼠逆转录病毒感染中对控制中和抗体产生的基因在15号染色体上的定位,我们对42名暴露于HIV-1但未感染的意大利人在人类22号染色体同线性区段的多态性位点进行基因分型,并通过封闭检验程序将他们与49名HIV-1感染个体和47名未感染的健康对照个体进行比较。
发现22号染色体q12-13基因型与一个推定的显性位点之间存在显著关联,该位点赋予暴露但未感染个体抗HIV-1免疫反应。暴露但未感染个体与其他两个表型组之间,22号染色体上连锁不平衡的分布也有所不同。
数据表明存在一个与暴露于HIV-1但未感染状态相关的新遗传因素。