Khaleduzzaman Mohammed, Francis Joseph, Corbin Meryll E, McIlwain Elizabeth, Boudreaux Marc, Du Min, Morgan Tim W, Peterson Karin E
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
J Virol. 2007 Nov;81(22):12307-15. doi: 10.1128/JVI.01002-07. Epub 2007 Sep 12.
Viral infections of the heart are a causative factor of myocarditis as well as of sudden, unexpected deaths of children, yet the mechanisms of pathogenesis remain unclear, in part due to the relatively few animal models of virus-induced myocarditis. In the current study, we examined the ability of polytropic murine retroviruses to infect the heart and induce cardiac dysfunction. In situ hybridization and immunohistochemistry analysis detected virus-infected cardiomyocytes and macrophages in the heart. A significant decrease in left ventricle function, as measured by fractional shortening, was detected in mice infected with the neurovirulent retrovirus Fr98 but not in mice infected with the nonneurovirulent retrovirus Fr54. Virus infection was not associated with consistent findings of fibrosis or substantial cellular infiltrate. Fr98-induced left ventricle dysfunction was associated with a higher virus load, increased mRNA expression of the macrophage marker F4/80, increased chemokine production, and a small number of apoptotic cells in the heart.
心脏病毒感染是心肌炎以及儿童突发意外死亡的一个致病因素，然而发病机制仍不清楚，部分原因是病毒诱导的心肌炎动物模型相对较少。在本研究中，我们检测了多嗜性鼠逆转录病毒感染心脏并诱导心脏功能障碍的能力。原位杂交和免疫组化分析在心脏中检测到病毒感染的心肌细胞和巨噬细胞。通过缩短分数测量，感染神经毒性逆转录病毒Fr98的小鼠左心室功能显著下降，但感染非神经毒性逆转录病毒Fr54的小鼠未出现此情况。病毒感染与纤维化或大量细胞浸润的一致表现无关。Fr98诱导的左心室功能障碍与更高的病毒载量、巨噬细胞标志物F4/80的mRNA表达增加、趋化因子产生增加以及心脏中少量凋亡细胞有关。
