Freel Stephanie A, Fiscus Susan A, Pilcher Christopher D, Menezes Prema, Giner Julieta, Patrick Ericka, Lennox Jeffrey L, Hicks Charles B, Eron Joseph J, Shugars Diane C
School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
AIDS. 2003 Sep 26;17(14):2025-33. doi: 10.1097/00002030-200309260-00003.
To determine whether oral fluids can serve as a model for studying HIV-1 shedding, we compared the genetic diversity, coreceptor use, and syncytium-inducing (SI) phenotype of viral variants in saliva and blood during primary HIV-1 infection.
Observational cross-sectional cohort study.
Blood plasma and saliva were sampled from 17 men early in primary HIV-1 infection. Viral diversity, predicted X4/R5 genotype and SI phenotype in samples were determined by heteroduplex tracking assays (HTAs) targeting the V1/V2 and V3 gp120 regions, sequence analyses and MT-2 cell assay.
Identical or very similar HTA banding and deduced amino acid sequence patterns in the V1/V2 and V3-encoding regions were observed between paired fluids of each subject. As assessed by V1/V2 HTA, 10 subjects had a single major viral variant and seven subjects exhibited multiple yet highly related variants. Two subjects had V1/V2 variants in blood that were identical to saliva but present in different relative abundances. A sexual transmission pair exhibited genetically dissimilar variants, suggesting transmission of a minor variant or rapid evolution during initial viremia. All subjects harbored R5 non-SI variants.
Relatively homogenous viral populations detected in plasma and saliva prior to seroconversion suggests that HIV-1 is disseminated to oral fluids early in infection and reflects the quasispecies in blood. These findings suggest that the oral cavity may serve as an easily accessible surrogate model for studying the dynamics of HIV-1 shedding at mucosal sites.
为了确定口腔液体是否可作为研究HIV-1脱落的模型,我们比较了初次HIV-1感染期间唾液和血液中病毒变体的基因多样性、共受体使用情况以及合胞体诱导(SI)表型。
观察性横断面队列研究。
在17名男性初次HIV-1感染早期采集血浆和唾液样本。通过针对V1/V2和V3 gp120区域的异源双链追踪分析(HTA)、序列分析和MT-2细胞试验来确定样本中的病毒多样性、预测的X4/R5基因型和SI表型。
在每个受试者的配对液体之间,观察到V1/V2和V3编码区域中相同或非常相似的HTA条带和推导的氨基酸序列模式。通过V1/V2 HTA评估,10名受试者有单一主要病毒变体,7名受试者表现出多个但高度相关的变体。两名受试者血液中的V1/V2变体与唾液中的相同,但相对丰度不同。一对性传播感染者表现出基因不同的变体,提示在初始病毒血症期间传播了次要变体或快速进化。所有受试者均携带R5非SI变体。
在血清转化之前在血浆和唾液中检测到的相对同质的病毒群体表明,HIV-1在感染早期就传播到口腔液体中,并反映了血液中的准种。这些发现表明,口腔可能是一个易于获取的替代模型,用于研究HIV-1在黏膜部位脱落的动态变化。