Determining Whether Transient HIV Infection Occurs

确定是否发生暂时性 HIV 感染

• 批准号: 7270580
• 负责人: Miles W. Cloyd
• 金额: $ 36.66万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-04 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270580
• 关键词: Acute; Adenovirus Infections; Adult; Antibodies; Appearance; Behavioral; Blood specimen; Case Study; Cohort Studies; Data; Distant; Documentation; Epitopes; Frequencies; Genetic Identity; Genital system; HIV; HIV Infections; HIV antibody positive; Hepatitis B; Hepatitis C; Immune response; Individual; Infant; Infection; Left; Liquid substance; Longitudinal Studies; Measles virus; Molecular Conformation; Monitor; Mothers; Nested PCR; Oral Sex; Peripheral Blood Lymphocyte; Peripheral Blood Mononuclear Cell; Phylogenetic Analysis; Polymerase Chain Reaction; Reporting; Rest; Risk; Sampling; Sequence Analysis; Serological; Serum; Source; Study Section; Testing; Time; Tonsil; Uncertainty; Virus; Virus Diseases; father role; gp160; nef Genes; sex; statistics

DESCRIPTION (provided by applicant): We have both old and more recent data which indicate that adults at high risk for HIV infection may sometimes become transiently infected with HIV. This includes: (1) transient appearance of serum antibodies (Ab) to conformational epitopes to gp41/gp160; (2) transient appearance of HIV in the PBMCs at the same time as Ab in some of the cases; (3) paternity typing of PBMC samples taken at the time of Ab and virus positivity, and later, when the subject is negative for both, thereby showing that they are from the same subject; (4) sequence analysis of the viruses present in transiently infected subjects, showing that they are not lab contaminants; and (5) demonstration in one case in which the virus in a transiently infected subject was genetically related to the virus in genital fluids from his HIV+ partner. Longitudinal statistics from studies of 37 high-risk subjects over 4 years showed that putative transient infections were more frequent than progressive infections and that the former was associated with unprotected oral sex, while the later was associated with unprotected genital sex. HIV was found by PCR in the tonsil of one such transiently HIV infected subject, but it was not detected in the PBMCs. We hypothesize that transient HIV infections do occur in high-risk adults, and we will focus this project only on proving or disproving this hypothesis. Our specific aims iare 1) to longitudinally screen at every 2-3 months 300 high-risk subjects for serological evidence of HIV infection; (2) attempt to detect HIV in the Ab-positive subjects and their source partners by nested PCR and PBMC culture; (3) sequence env and nef genes that are amplified and perform phylogenetic analyses to show relatedness between viruses in putative transiently infected subjects and their source partners; and (4) demonstrate that blood samples have not been mixed up. Although transient infection is presently controversial, our data indicate that it occurs and we will attempt to prove it.

描述（由申请人提供）：我们有旧的和最新的数据表明，艾滋病毒感染高危成年人有时可能会暂时感染艾滋病毒。这包括： (1) 短暂出现针对 gp41/gp160 构象表位的血清抗体 (Ab)； (2) 某些病例中，HIV 与 Ab 同时短暂出现在 PBMC 中； (3) 在抗体和病毒呈阳性时以及随后当受试者两者均为阴性时采集的 PBMC 样本进行亲子鉴定，从而表明它们来自同一受试者； (4) 对短暂感染受试者体内存在的病毒进行序列分析，表明它们不是实验室污染物； (5) 在一个案例中证明，短暂感染者体内的病毒与其 HIV+ 伴侣生殖器液体中的病毒在遗传上相关。对 37 名高危受试者历时 4 年研究的纵向统计显示，假定的短暂性感染比进行性感染更常见，并且前者与无保护的口交有关，而后者与无保护的生殖器性行为有关。通过 PCR 在一名短暂感染 HIV 的受试者的扁桃体中发现了 HIV，但在 PBMC 中未检测到。我们假设短暂性艾滋病毒感染确实发生在高危成年人中，我们将仅将这个项目的重点放在证明或反驳这一假设上。我们的具体目标是 1) 每 2-3 个月对 300 名高危受试者进行纵向筛查，以获取 HIV 感染的血清学证据； (2)尝试通过巢式PCR和PBMC培养来检测抗体阳性受试者及其来源伴侣中的HIV； (3) 对 env 和 nef 基因进行测序，这些基因被扩增并进行系统发育分析，以显示假定的短暂感染受试者及其源伙伴中的病毒之间的相关性； (4) 证明血液样本没有混合。尽管暂时性感染目前存在争议，但我们的数据表明它确实存在，我们将尝试证明这一点。