Vilela Márcia Carvalho, Mansur Daniel Santos, Lacerda-Queiroz Norinne, Rodrigues David Henrique, Lima Graciela Kunrath, Arantes Rosa Maria Esteves, Kroon Erna Geessien, da Silva Campos Marco Antônio, Teixeira Mauro Martins, Teixeira Antônio Lúcio
Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Ann N Y Acad Sci. 2009 Feb;1153:256-63. doi: 10.1111/j.1749-6632.2008.03959.x.
The Herpes simplex virus-1 (HSV-1) is responsible for several clinical manifestations in humans, including encephalitis. To induce encephalitis, C57BL/6 mice were inoculated with 10(4) plaque-forming cells of HSV-1 by the intracranial route. Met-RANTES (regulated upon activation, normal T cell expressed and presumably secreted) (10 microg/mouse), a CC chemokine family receptor (CCR)1 and CCR5 antagonist, was given subcutaneously the day before, immediately after, and at days 1, 2, and 3 after infection. Treatment with Met-RANTES had no effect on the viral titers. In contrast, intravital microscopy revealed that treatment with Met-RANTES decreased the number of leukocytes adherent to the pial microvasculature at days 1 and 3 after infection. The levels of the chemokines CCL3, CCL5, CXCL1, and CXCL9 increased after infection and were enhanced further by the treatment with Met-RANTES. Treatment with a polyclonal anti-CCL5 antibody 2 h before the intravital microscopy decreased leukocyte adhesion in the microcirculation of infected mice. In conclusion, CCL5, a chemokine that binds to CCR1 and CCR5, is essential for leukocyte adhesion during HSV-1 encephalitis. However, blocking of CCR1 and CCR5 did not affect HSV-1 replication, suggesting that other immune mechanisms are involved in the process of infection control.
单纯疱疹病毒1型（HSV-1）可引发人类的多种临床表现，包括脑炎。为诱发脑炎，通过颅内途径给C57BL/6小鼠接种10⁴个HSV-1蚀斑形成细胞。Met-RANTES（活化时表达、正常T细胞表达且可能分泌的调节因子）（10微克/小鼠），一种CC趋化因子家族受体（CCR）1和CCR5拮抗剂，在感染前一天、感染后即刻以及感染后第1、2和3天皮下给药。Met-RANTES治疗对病毒滴度没有影响。相比之下，活体显微镜检查显示，Met-RANTES治疗在感染后第1天和第3天减少了附着于软脑膜微血管的白细胞数量。趋化因子CCL3、CCL5、CXCL1和CXCL9的水平在感染后升高，并且通过Met-RANTES治疗进一步增强。在活体显微镜检查前2小时用多克隆抗CCL5抗体治疗可减少感染小鼠微循环中的白细胞黏附。总之，一种与CCR1和CCR5结合的趋化因子CCL5，在HSV-1脑炎期间对白细胞黏附至关重要。然而，阻断CCR1和CCR5并不影响HSV-1复制，这表明在感染控制过程中涉及其他免疫机制。
