基孔肯雅（Chikungunya）病毒

《实验医学》杂志电子版2月1日发表了一项研究，表明抗病毒蛋白1型干扰素对抵抗外源的蚊媒基孔肯雅（Chikungunya）病毒是必需的。

基孔肯雅病毒可以导致高烧和严重的关节疼痛，近期内在南非流行，某些地方有超过30%的人被感染。

巴黎巴斯德研究所的Marc Lecuit和Matthew Albert研究小组发现感染基孔肯雅病毒的患者血液中的1型干扰素含量上升。与基孔肯雅病毒相关的病毒主要激发免疫细胞产生1型干扰素，而在基孔肯雅病毒感染中免疫细胞既不产生1型干扰素，对其也不反应。成纤维细胞（主要的感染细胞）产生必需的1型干扰素。将来的抗基孔肯雅病毒感染治疗需要考虑这一特性。

原始出处：

The Journal of Experimental Medicine doi:10.1084/jem.20090851

Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

Clémentine Schilte1,7, Thérèse Couderc3,8, Fabrice Chretien6,9, Marion Sourisseau4,10, Nicolas Gangneux3,8, Florence Guivel-Benhassine4,10, Anton Kraxner1,7, Jürg Tschopp11, Stephen Higgs12, Alain Michault13, Fernando Arenzana-Seisdedos5,10, Marco Colonna14, Lucie Peduto2, Olivier Schwartz4,10, Marc Lecuit3,8,15,16, and Matthew L. Albert1,7,16

1 Department of Immunology, Unité Immunobiologie des Cellules Dendritiques and 2 Laboratory of Lymphoid Tissue Development, 3 Department of Infection and Epidemiology, Groupe Microorganismes et Barrières de l’H?te, 4 Department of Virology, Unité Virus et Immunité, 5 Unité de Pathogénie Virale Moléculaire, and 6 Department of Development, unité cellules souches et développement, Institut Pasteur, 75724 Paris, Cedex 15, France
7 Institut National de la Santé et de la Recherche Médicale (INSERM) U818, 8 équipe avenir INSERM U604, and 9 INSERM U955, H?pital Henri Mondor and Faculté de Médecine Paris-12, 94010 Créteil, France
10 Centre National de la Recherche Scientifique URA 3015, 75724 Paris, France
11 Department of Biochemistry, Université de Lausanne, CH-1066 Epalignes, Switzerland
12 University of Texas Medical Branch, Galveston, TX 77555
13 Laboratoire de Microbiologie, Groupe Hospitalier Sud Réunion, 97448 Saint-Pierre, France
14 Department of Immunology, Washington University, St Louis, MO 63130
15 Division of Infectious Diseases, H?pital Necker Enfants malades, 75015 Paris, France
16 Université Paris Descartes, 75006 Paris, France

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR–/–WT bone marrow chimeras are capable of clearing the infection, whereas WTIFNAR–/– chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.