急性期HIV病毒主要利用CXCR4辅助受体与疾病快速进展密切相关

Coreceptor CXCR4 and rapid disease progression in acute HIV infection

目的探讨急性HIV-1感染中病毒嗜性对疾病进展的影响以及在HIV感染最初一年中病毒嗜性的变化。方法 12例急性HIV-1感染者来源于首都医科大学附属北京佑安医院男男性接触者(MSM)高危人群队列,其中7例病情进展较快(感染HIV 2年后CD4+T细胞计数<200个/μl),5例病情进展较慢(感染HIV 2年后CD4+T细胞计数仍>500个/μl)。留取患者第一次HIV阳性随访点和48周随访点血浆标本,提取病毒基因组RNA,克隆HIV-1 env区的C2～V5区并测序。用Geno2pheno和PSSM软件预测共受体嗜性。结果成功克隆和测序的病毒株中,7例快速进展患者HIV感染后第一次随访时X4嗜性病毒株比例为87.0%(80/92),R5嗜性病毒株比例为13.0%(12/92);感染HIV 1年时X4嗜性病毒株占91.2%(93/102),R5嗜性病毒株占8.8%(9/102)。5例病情进展缓慢者,HIV感染后第一次随访时X4嗜性病毒株所占的比例为4.8%(3/62),R5嗜性病毒株所占的比例为95.2%(59/62);HIV感染1年时X4嗜性病毒株占5.2%(3/58),R5嗜性病毒株占94.8%(55/58)。结论 CXCR4嗜性毒株可能与HIV-1感染早期疾病进展有关,在感染第一年病毒嗜性无明显变化。

Objective To investigate the impact of HIV-1 coreceptor tropism on disease progression and the changes of viral tropism during the first year of HIV infection. Methods Twelve patients with acute HIV 1 in- fection including 7 cases of rapid progression and 5 of slow progression were enrolled from a high risk men who have sex with men （MSM） cohort in our hospital. Viral RNA was extracted from the plasma of these patients at the first visit being detected HIV positive and 48 weeks thereafter. The C2-V5 regions of the HIV-1 env gene were cloned and sequenced. Viral tropism was predicated hased on the V3 loop amino acid sequences using Geno2pheno and PSSM programs. Results At the first visit of the acute HIV infection, virus strains with CX- CR4 tropism in cases of rapid progression accounted for 87.0% （80/92） and strains with CCR5 tropism in pa- tients of slow progression accounted for 95.2% （59/62） ;48 weeks later, these two rates changed to 91.2% （93/102） and 94.8% （55/58）, respectively. Conclusions CXCR4 tropism strongly associated with the early disease progression of HIV-1 infection and keeps relatively constant during the first year of infection.