Murine Coronavirus-Induced Subacute Fatal Peritonitis in C57BL/6 Mice Deficient in Gamma Interferon

Gamma interferon-deficient (IFN-γ−/−) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-γ-+/− and IFN-γ+/+ mice, JHMV persisted in IFN-γ−/− mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-γ−/− mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-γ protracted the survival time of IFN-γ−/− mice after JHMV infection. These results demonstrate that IFN-γ plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-γ−/− mice, which bears a resemblance to feline infectious peritonitis in cats.

以C57BL/6遗传背景的γ干扰素缺陷型（gamma interferon-deficient，IFN-γ−/−）小鼠为研究对象，经腹腔途径接种小鼠肝炎病毒JHM株（JHMV）。与IFN-γ+/-及IFN-γ+/+小鼠相比，JHMV可在IFN-γ−/−小鼠体内持续存在，并在感染亚急性期引发宿主死亡。意外的是，感染后的IFN-γ−/−小鼠在感染亚急性期出现重度腹膜炎，伴随腹腔与胸腔内黏性积液蓄积，且未观察到肝细胞出现破坏性病变。重组IFN-γ给药可延长JHMV感染后IFN-γ−/−小鼠的存活时长。上述实验结果证实，IFN-γ在JHMV感染的病毒清除过程中发挥关键作用；同时研究发现，持续存在的JHMV感染会在IFN-γ−/−小鼠中诱发一种新型疾病表型，该表型与猫的猫传染性腹膜炎（feline infectious peritonitis）高度相似。