Vázquez Manuel, Maldonado Irvin M, Almodóvar Sharilyn, López Carlos, Colón María Del C, Hill Martin, Lorenzo Eric
Molecular Virology Laboratory, Department of Physiology and Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico.
AIDS Res Hum Retroviruses. 2010 Apr;26(4):471-9. doi: 10.1089/aid.2009.0109.
Monocytes serve as a systemic reservoir of myeloid precursors for the renewal of tissue macrophages and dendritic cells (DCs). Both monocytes and dendritic cells can be infected with HIV-1. Circulating DCs are believed to be derived from a common precursor of monocytes, or, in the case of inflammatory challenge, from monocytes directly. Because there are fewer infected blood monocytes than infected cells after differentiation, we hypothesized that the majority of HIV-1 infection in circulating DCs occurs via direct viral binding to their CD4 and coreceptors after differentiation. We isolated monocytes at one time point and circulating dendritic cells at a second time point from the blood of HIV-1-infected patients. Proviral DNA was isolated from DCs and monocytes, and the C2-V4 region of the HIV-1 env gene was cloned and sequenced. Phylogeny, nucleotide distances, and glycosylation patterns of the env gene were performed. The phylogenetic trees revealed that viral forms from the monocytes clustered distantly from the quasispecies derived from circulating DCs. The nucleotide distances and differing glycosylation patterns suggest that the infection of DCs is independent of the infection of the monocytes.
单核细胞作为髓系前体细胞的全身储存库，用于组织巨噬细胞和树突状细胞（DC）的更新。单核细胞和树突状细胞都可被HIV-1感染。循环中的DC被认为来源于单核细胞的共同前体，或者在炎症刺激的情况下，直接来源于单核细胞。由于分化后被感染的血液单核细胞比被感染的细胞少，我们推测循环DC中大多数HIV-1感染是在分化后通过病毒直接与其CD4和共受体结合而发生的。我们在一个时间点从HIV-1感染患者的血液中分离出单核细胞，在第二个时间点分离出循环树突状细胞。从DC和单核细胞中分离出前病毒DNA，并对HIV-1 env基因的C2-V4区域进行克隆和测序。对env基因进行了系统发育、核苷酸距离和糖基化模式分析。系统发育树显示，来自单核细胞的病毒形式与来自循环DC的准种聚类较远。核苷酸距离和不同的糖基化模式表明，DC的感染独立于单核细胞的感染。
