Transient HIV Infection: Its Underlying Mechanisms

虽然有一些报告的情况下，短暂的艾滋病毒感染的成人和婴儿出生的艾滋病毒阳性的母亲，最近重新评估的许多存储的PBMC样本从婴儿的情况下，表明很少有确凿的证据表明，短暂的感染曾经发生。我们现在有迄今为止最好的证据表明，短暂感染确实发生在成人中，通过两项独立的测试（gp 160构象表位的血清抗体[Ab]和PBMC中病毒的直接存在）显示，在4年的时间内研究的大约20%的EIA阴性，高风险个体至少有一次短暂感染。抗体和病毒可检测1-3个月，然后两者都消失。我们通过亲子鉴定分型表明，在短暂阳性时采集的PBMC样本和随后阴性时采集的PBMC样本来自同一个体。我们还发现，存在于几个短暂感染受试者的PBMC中的病毒不是实验室污染物。我们目前的假设是，短暂的艾滋病毒感染确实在高危成人中发生的频率很高，这可能是由于感染后立即诱导的某些类型的免疫反应的存在，以及某些对病毒感染或传播产生负面影响的宿主基因。本文提出了四个具体的目标来解决这一假设：1）进一步证实短暂的HIV感染并描述其在高危成人中的流行病学频率; 2）定量短暂感染期间存在的HIV中和和ADCC抗体反应活性; 3）评估T-在病毒阳性时和病毒不能被检测到的较晚时间点，瞬时感染个体的细胞反应;以及4）表征在短暂感染期间存在的HIV毒株，并评估已知影响HIV的基因的宿主基因型。很明显，理解为什么有些人可以自发地消除艾滋病毒，而其他人不能，如果它是免疫介导的，那么这将是开发保护性疫苗的重要基础信息。

Although there have been a number of reports of cases of transient HIV infection in both adults and babies born to HIV+ mothers, a recent re-evaluation of many of the stored PBMC samples from infant cases indicated that there was little solid evidence that transient infection ever occurred. We now have the best evidence to date that transient infection does occur in adults, showing by two independent tests (serum antibodies [Ab] to conformational epitopes of gp160 and direct presence of virus in PBMC) that approximately 20% of EIA-negative, high-risk individuals studied over a 4-year period become transiently infected at least one time. The Ab and virus are detectable for 1-3 months, and then both disappear. We showed by paternity typing that PBMC samples taken at the time of transient positivity, and later when negative, were from the same invividual. We also showed that the viruses present in PBMCs of several transiently infected subjects were not laboratory contaminants. Our current hypothesis is that transient HIV infection does occur at significant frequencies in high-risk adults, and is probably due to the presence of certain types of immune responses induced immediately after infection, as well as certain host genes which negatively influence either virus infection or spread. Four Specific Aims are proposed to address this hypothesis: 1) to further substantiate transient HIV infection and delineate its epidemiological frequencies in high-risk adults; 2) to quantitate HIV neutralizing and ADCC activities of the antibody responses present during transient infection; 3) to assess the T-cell responses in transiently infected individuals at the time of virus positivity and at later time points when virus cannot be detected; and 4) to characterize the HIV strains present during the period of transient infection, and to assess the host genotype for genes known to influence HIV. It obviously would be important to understand why some individuals can spontaneously eliminate HIV, while others cannot, and if it is immune-mediated, then this would be important fundamental information for developing a protective vaccine.