Section of Intercellular Interactions, Eunice-Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Infect Dis. 2012 Jan 1;205(1):97-105. doi: 10.1093/infdis/jir700. Epub 2011 Nov 22.
Semen is the main carrier of sexually transmitted viruses, including human immunodeficiency virus type 1 (HIV-1). However, semen is not just a mere passive transporter of virions but also plays an active role in HIV-1 transmission through cytokines and other biological factors.
To study the relationship between viruses and the chemokine-cytokine network in the male genital tract, we measured the concentrations of 21 cytokines/chemokines and the loads of HIV-1 and of 6 herpesviruses in seminal and blood plasma from HIV-1-infected and HIV-uninfected men.
We found that (1) semen is enriched in cytokines and chemokines that play key roles in HIV-1 infection or transmission; (2) HIV-1 infection changes the chemokine-cytokine network in semen, further enriching it in cytokines that modulate its replication; (3) HIV-1 infection is associated with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) compartmentalized seminal reactivation; (4) CMV and EBV concomitant seminal shedding is associated with higher HIV-1 loads in blood and seminal plasma; and (5) CMV seminal reactivation increases the seminal levels of the CCR5 ligands RANTES and eotaxin, and of the CXCR3 ligand monokine induced by gamma interferon (MIG).
HIV-1 infection results in an aberrant production of cytokines and reactivation of EBV and CMV that further changes the seminal cytokine network. The altered seminal milieu in HIV-1 infection may be a determinant of HIV-1 sexual transmission.
精液是包括人类免疫缺陷病毒 1 型(HIV-1)在内的性传播病毒的主要载体。然而,精液不仅仅是病毒粒子的被动运输者,还通过细胞因子和其他生物因素在 HIV-1 传播中发挥积极作用。
为了研究病毒与男性生殖道中趋化因子-细胞因子网络之间的关系,我们测量了 21 种细胞因子/趋化因子以及 HIV-1 和 6 种疱疹病毒在 HIV-1 感染和未感染男性的精液和血浆中的载量。
我们发现:(1)精液富含在 HIV-1 感染或传播中发挥关键作用的细胞因子和趋化因子;(2)HIV-1 感染改变了精液中的趋化因子-细胞因子网络,进一步富集了调节其复制的细胞因子;(3)HIV-1 感染与 EBV 和 CMV 分隔的精液重新激活有关;(4)CMV 和 EBV 同时在精液中排出与血液和精液血浆中 HIV-1 载量更高有关;(5)CMV 精液重新激活增加了 CCR5 配体 RANTES 和 eotaxin 以及γ干扰素诱导的单核细胞趋化蛋白(MIG)的精液水平。
HIV-1 感染导致细胞因子的异常产生和 EBV 和 CMV 的重新激活,进一步改变了精液中的细胞因子网络。HIV-1 感染中改变的精液环境可能是 HIV-1 性传播的决定因素。