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人体对HIV-1的易感性,除病毒本身和个体的行为因素外,宿主的遗传因素,即遗传变异起了重要作用.一些个体的不感染和长期不进展现象完全是由于宿主本身的遗传背景造成的,而非药物.在过去的10年中,有关宿主的遗传多态性与HIV感染、AIDS病程进展、抗HIV药物治疗效果和毒性的研究已成为HIV研究的热点.宿主的遗传因素主要通过作用于病毒入侵细胞形成感染这一过程和修饰机体的免疫反应而影响对HIV的易感性和AIDS病程的进展.这些遗传变异主要包括细胞因子受体和配体系统基因及HLA和抗原呈递系统基因.前者有CCR5,CCR2,SDF1,IL10,RANTES,IFN-γ和CXCR6等.后者包括HLA-B~*57,HLA-B~*27和HLA-B~*35等.其中CCR5和CCR2的变异是研究得最透彻的.CCR5基因编码区32个碱基的纯合性缺失(CCR5△32)可完全保护携带者不感染HIV,杂合性缺失可延迟感染后病程的进展;CCR5△32还有利于抗病毒治疗.对宿主遗传背景的的研究不仅可以理解HIV的自然感染过程,对病情的预测、抗HIV药物的开发、治疗策略的制定及疫苗研究都有指导意义.目前CD4阳性T细胞计数、HIV病毒载量、CD4阳性T细胞耗竭速度及AIDS临床症状是临床上判断病情的依据,而没有考虑可能起重要作用的宿主因素.最近的研究表明,HIV抑制因子CCL3L1(MIP-1αP)基因的拷贝数与个体HIV-1/AIDS的易感性相关.拥有的CCL3L1拷贝数越少,对HIV-1越易感.每多一个拷贝就可降低4.5%～10.5%HIV感染的风险.这使得通过筛查CCL3L1剂量,结合其他宿主基因分型如CCR5,预测个体对HIV/AIDA的易感程度、指导临床治疗成为真正的可能.
Human susceptibility to HIV-1, in addition to the virus itself and individual behavioral factors, the host genetic factors, that genetic variation plays an important role in some individuals not infected and long-term non-progress completely due to the host’s own genetic background Caused by, but not drugs.In the past 10 years, studies on genetic polymorphisms of hosts and HIV infection, progression of AIDS, anti-HIV drug treatment effect and toxicity have become hot spots in HIV research.The genetic factors of host are mainly Influences on the susceptibility to HIV and on the progression of AIDS are influenced by the process of infection by viruses that invade cells and the modification of the body’s immune response.These genetic variations mainly include the cytokine receptor and ligand system genes and HLA and antigen presenting system The former includes CCR5, CCR2, SDF1, IL10, RANTES, IFN-γ and CXCR6 etc. The latter includes HLA-B * 57, HLA-B * 27 and HLA-B * (CCR5 △ 32) completely protects the carrier from HIV infection, and the loss of heterozygosity can delay the progression of the disease after infection.CCR5 △ 32 is also good for antiviral treatment The research of the main genetic background not only can understand the process of natural HIV infection but also guide the prediction of the disease, the development of anti-HIV drugs, the formulation of therapeutic strategies and vaccine research.Currently, CD4 positive T cell count, HIV viral load, The rate of depletion of CD4-positive T cells and the clinical features of AIDS are the basis for clinical judgment of the condition, without considering the possible host factors.Recent studies have shown that the copy number of the HIV inhibitory factor CCL3L1 (MIP-1αP) -1 / AIDS, with fewer copies of CCL3L1 and more susceptible to HIV-1, with one more copy reducing the risk of HIV infection by 4.5% to 10.5%, making it possible to screen for CCL3L1 doses, Combined with other host genotyping such as CCR5, to predict individual susceptibility to HIV / AIDA, to guide the clinical treatment has become a real possibility.