Dutia B M, Clarke C J, Allen D J, Nash A A
Department of Veterinary Pathology, University of Edinburgh, Summerhall, United Kingdom.
J Virol. 1997 Jun;71(6):4278-83. doi: 10.1128/JVI.71.6.4278-4283.1997.
Murine gammaherpesvirus is a natural rodent pathogen which causes a primary infection in the lungs and establishes a persistent infection in B lymphocytes. During the primary infection, large amounts of gamma interferon (IFN-gamma) are produced by spleen, mediastinal, and cervical lymph node cells. To investigate the role of IFN-gamma in control of the virus infection, mice lacking the cellular receptor for IFN-gamma (IFN-gamma R-/- mice) were infected with murine gammaherpesvirus 68 (MHV68). IFN-gamma R-/- mice showed no difference from wild-type mice in the titers of infectious virus in the lungs or in the rate of clearance of the lung infection. In the spleen, however, clear differences were observed. By 14 days postinfection, spleens from IFN-gamma R-/- mice were pale, shrunken, and fibrous. Histological examination showed that there was an early (day 10) infiltration of granulocytes followed by widespread destruction of splenic architecture (days 14 to 17). A marked decrease in the number of splenic B cells and CD4+ and CD8+ T cells occurred. These changes were accompanied by a 10- to 100-fold greater load of latently infected cells in IFN-gamma R-/- mice than in wild-type mice at 14 to 17 days postinfection, but this was reduced to the levels found in wild-type mice by 21 days postinfection. Treatment of the mice with the antiviral drug 2'-deoxyl-5-ethyl-beta-4'-thiouridine from 6 days postinfection did not prevent the occurrence of these changes. The changes were, however, completely reversed by depletion of CD8+ T cells prior to and during the primary infection. Depletion of CD4+ T cells also reversed the major pathological and virological changes, although in this case there was evidence of some histological changes. Thus, the lack of IFN-gamma receptor had profound consequences in spleens of MHV68-infected mice. The possible mechanisms involved in these changes are discussed.
小鼠γ疱疹病毒是一种天然的啮齿动物病原体，它在肺部引发原发性感染，并在B淋巴细胞中建立持续性感染。在原发性感染期间，脾脏、纵隔和颈部淋巴结细胞会产生大量的γ干扰素（IFN-γ）。为了研究IFN-γ在控制病毒感染中的作用，将缺乏IFN-γ细胞受体的小鼠（IFN-γR-/-小鼠）用小鼠γ疱疹病毒68（MHV68）进行感染。IFN-γR-/-小鼠在肺部感染性病毒滴度或肺部感染清除率方面与野生型小鼠没有差异。然而，在脾脏中观察到了明显的差异。感染后14天，IFN-γR-/-小鼠的脾脏苍白、萎缩且纤维化。组织学检查显示，早期（第10天）有粒细胞浸润，随后脾脏结构广泛破坏（第14至17天）。脾脏B细胞以及CD4+和CD8+T细胞数量显著减少。这些变化伴随着在感染后14至17天，IFN-γR-/-小鼠中潜伏感染细胞的负荷比野生型小鼠高10至100倍，但在感染后21天降至野生型小鼠的水平。从感染后6天开始用抗病毒药物2'-脱氧-5-乙基-β-4'-硫尿苷治疗小鼠并不能阻止这些变化的发生。然而，在原发性感染之前和期间通过消耗CD8+T细胞，这些变化完全得到了逆转。消耗CD4+T细胞也逆转了主要的病理和病毒学变化，尽管在这种情况下有一些组织学变化的证据。因此，缺乏IFN-γ受体对感染MHV68的小鼠脾脏产生了深远的影响。文中讨论了这些变化可能涉及的机制。
