基因变异：增加艾滋病毒感染，减慢艾滋病发病

2001年7月26日 家庭医生医疗保健网

　　路透社纽约健康消息-根据《艾滋病》杂志电子网络版的一篇报导，人体基因的每个细微变异，都可引起感染艾滋病病毒的可能性增加；但一旦被感染，发展为艾滋病的过程却又可因此而被减慢。

　　美国国家过敏和传染病研究所大卫·麦德莫特博士及其同事对被艾滋病病毒感染及对艾滋病有抵抗力的人体内一种名叫兰特(RANTES)的基因变异进行了观察，从中寻找那些被称为单核苷酸多形化(SNPs)的细微变异。结果发现，此类SNP变化出现在HIV阳性的人身上比出现在对HIV有抵抗力的人身上明显多得多，同时这一特别的变化增加了RANTES基因的活动性；并且具有这种SNP变异的人感染HIV的机会比常人增加两倍。然而，具有这种SNP变化的人感染了HIV之后发展到艾滋病的时间却延长了40%。

　　出现这种奇异的现象的原因尚不清楚。麦德莫特认为，这种特殊的SNP变化可能会导致过量生产兰特基因免疫系统分子。这些分子引起炎性反应，增加了细胞间隙，从而令HIV病毒更易进入机体。而另一方面，因为兰特基因免疫系统分子首先吸附在T细胞受体，阻碍病毒的吸附而减慢HIV病毒对机体的侵蚀。

　　麦德莫特指出，基于兰特基因疗法可减慢HIV的传播，几个公司正在尝试开发兰特基因。但研究者必须注意，兰特基因分子水平过高又可增加获得HIV的可能性。

　　高级研究员菲利普·M·莫菲的实验室目前正在进行进一步的实验以明确兰特基因分子的作用机制。其它研究者年内将开始进行临床试验。总有一天，我们会弄清楚所有影响个人对HIV易感性的基因变异。到那时，医生就可据此判断每个人对病毒的易感性。

　　来源：《艾滋病》2000；14：2671-2678

　　New Genetic Risk Factor for HIV Found

　　NEW YORK (Reuters Health) - A small genetic variation appears to increase susceptibility to HIV infection， but slow progression to AIDS (news - web sites) once infected， according to a new report in the online edition of the journal AIDS.

　　Dr. David H. McDermott and colleagues at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda， Maryland and elsewhere， looked at variations in a gene called RANTES in HIV-infected and HIV-resistant people. Specifically， they looked for tiny changes known as single nucleotide polymorphisms (SNPs).

　　McDermott's group found that "one such SNP appears significantly more often in HIV-positive than HIV-resistant individuals，"and this particular alteration "increases the activity of the RANTES gene and is associated with up to twice the risk of HIV infection。”However， "individuals with this SNP who become infected with HIV take about 40% longer to develop AIDS.‘‘

　　The reason for this paradoxical effect is not clear. McDermott suggests that this specific SNP may cause overproduction of the RANTES immune system molecule. This molecule then creates an inflammatory response that widens the space between cells， which permits HIV to enter more easily. At the same time， an overabundance of this molecule， which attaches to T cell receptors， may slow HIV by blocking viral attachment——because RANTES gets there first.

　　"This study offers the first genetic evidence that RANTES affects the risk of HIV transmission，"Dr. Anthony S. Fauci， NIAID director， points out.

　　Several companies are trying to develop RANTES-based therapies to slow HIV progression， McDermott noted. "The results of our study support those efforts， but researchers must remember that higher RANTES levels may increase the likelihood of acquiring HIV，"he cautioned.

　　Senior investigator Dr. Philip M. Murphy told Reuters Health that the reason for the RANTES effect still needs to be clarified. Murphy's lab is currently working to understand the mechanisms involved. Other investigators will begin clinical trials within the year.

　　"Ultimately， understanding all the genetic variations that interact to affect one's response to HIV will one day allow doctors to create genetic profiles that quantify a person's susceptibility to the virus，"Murphy concluded.

　　Source： Aids 2000；14：2671-2678.