Zhu Jia, Hladik Florian, Woodward Amanda, Klock Alexis, Peng Tao, Johnston Christine, Remington Michael, Magaret Amalia, Koelle David M, Wald Anna, Corey Lawrence
Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Nat Med. 2009 Aug;15(8):886-92. doi: 10.1038/nm.2006. Epub 2009 Aug 2.
To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy. The CD4(+) T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies. The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition.
为探究单纯疱疹病毒2型（HSV-2）感染与获得性人类免疫缺陷病毒1型（HIV-1）之间的关联机制，我们对接受和未接受抗病毒治疗的患者的HSV-2病变进行了连续活检，并对细胞浸润情况进行了原位分析。即使每日进行抗病毒治疗，CD4(+)和CD8(+) T细胞以及包括表达C型凝集素受体DC-SIGN的细胞在内的浆细胞样和髓样树突状细胞（DC）混合群体，在HSV-2再激活部位愈合后仍持续存在数月。持续存在的CD4(+) T细胞对HSV-2抗原产生反应，趋化因子受体CCR5的表达增加，并且与表达白细胞介素-3受体CD123或DC-SIGN的DC相邻。用嗜CCR5的HIV-1毒株进行体外感染发现，与对照皮肤活检组织来源的细胞相比，愈合的生殖器病变活检组织来源的细胞中整合的HIV-1 DNA浓度更高。生殖器中HIV受体阳性炎性细胞的持续存在和富集有助于解释抗HSV-2治疗无法降低HIV感染率的原因。
