Heraud Jean-Michel, Merien Fabrice, Mortreux Frank, Mahieux Renaud, Kazanji Mirdad
Laboratoire de Rétrovirologie, Institut Pasteur de la Guyane, BP6010, 97306 Cayenne, French Guiana, France.
Virology. 2007 May 10;361(2):402-11. doi: 10.1016/j.virol.2006.11.028. Epub 2007 Jan 16.
We have developed an animal model of experimental HTLV-1 infection in Saimiri sciureus monkeys in order to study both the immunological and the virological aspects of the infection. As cytokines expressed by immune cells play an essential role during viral infection, we have studied the correlation between the expression of some Th1/Th2 cytokines, including IL-2, IL-5, IL-6, IL-10, and IFN-gamma, and immunological dynamics during primary and chronic HTLV-1 infection in this model. We first demonstrated that, during primary infection, IFN-gamma, IL-2 and IL-10 are expressed at different times and levels. The expression of these cytokines is concomitant with the increase in the numbers of CD4(+), CD8(+) and CD16(+) cells and with the presence of tax/rex viral mRNA. These data indicate the involvement of various cell types in the antiviral immune response. Subsequently, we showed that peripheral blood mononuclear cells freshly isolated from chronically infected monkeys express IFN-gamma and IL-6 at higher levels than those from uninfected animals. IFN-gamma expression is quantitatively correlated to the proviral load and to the presence of circulating effector T-cells against Tax peptide, as detected by Elispot. Further studies will be needed to determine the effective role of these cytokines and other immune system modulators in the control of viral replication during primary HTLV-1 infection or latency.
为了研究实验性人类嗜T淋巴细胞病毒1型(HTLV-1)感染的免疫学和病毒学方面,我们开发了松鼠猴实验性HTLV-1感染动物模型。由于免疫细胞表达的细胞因子在病毒感染过程中发挥着重要作用,我们研究了一些Th1/Th2细胞因子(包括白细胞介素-2(IL-2)、白细胞介素-5(IL-5)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和干扰素-γ(IFN-γ))的表达与该模型中HTLV-1原发性和慢性感染期间免疫动力学之间的相关性。我们首先证明,在原发性感染期间,IFN-γ、IL-2和IL-10在不同时间和水平表达。这些细胞因子的表达与CD4(+)、CD8(+)和CD16(+)细胞数量的增加以及tax/rex病毒mRNA的存在同时出现。这些数据表明多种细胞类型参与了抗病毒免疫反应。随后,我们发现从慢性感染猴子新鲜分离的外周血单核细胞比未感染动物的细胞表达更高水平的IFN-γ和IL-6。IFN-γ的表达在数量上与前病毒载量以及通过酶联免疫斑点法检测到的针对Tax肽的循环效应T细胞的存在相关。需要进一步研究以确定这些细胞因子和其他免疫系统调节剂在原发性HTLV-1感染或潜伏期控制病毒复制中的有效作用。