Zhou Haixia, Perlman Stanley
Department of Pediatrics, University of Iowa, Iowa City, 52242, USA.
J Virol. 2006 Mar;80(5):2506-14. doi: 10.1128/JVI.80.5.2506-2514.2006.
Mouse hepatitis virus strain JHM (MHV-JHM) causes acute encephalitis and acute and chronic demyelinating diseases in mice. Dendritic cells (DCs) are key cells in the initiation of innate and adaptive immune responses, and infection of these cells could potentially contribute to a dysregulated immune response; consistent with this, recent results suggest that DCs are readily infected by another strain of mouse hepatitis virus, the A59 strain (MHV-A59). Herein, we show that the JHM strain also productively infected DCs. Moreover, mature DCs were at least 10 times more susceptible than immature DCs to infection with MHV-JHM. DC function was impaired after MHV-JHM infection, resulting in decreased stimulation of CD8 T cells in vitro. Preferential infection of mature DCs was not due to differential expression of the MHV-JHM receptor CEACAM-1a on mature or immature cells or to differences in apoptosis. Although we could not detect infected DCs in vivo, both CD8(+) and CD11b(+) splenic DCs were susceptible to infection with MHV-JHM directly ex vivo. This preferential infection of mature DCs may inhibit the development of an efficient immune response to the virus.
小鼠肝炎病毒JHM株（MHV-JHM）可引起小鼠急性脑炎以及急性和慢性脱髓鞘疾病。树突状细胞（DCs）是启动先天性和适应性免疫反应的关键细胞，这些细胞的感染可能会导致免疫反应失调；与此一致的是，最近的结果表明DCs很容易被另一株小鼠肝炎病毒A59株（MHV-A59）感染。在此，我们表明JHM株也能有效感染DCs。此外，成熟DCs对MHV-JHM感染的易感性至少比未成熟DCs高10倍。MHV-JHM感染后DC功能受损，导致体外对CD8 T细胞的刺激减少。成熟DCs的优先感染并非由于成熟或未成熟细胞上MHV-JHM受体CEACAM-1a的差异表达，也不是由于凋亡差异。虽然我们在体内未检测到被感染的DCs，但CD8(+)和CD11b(+)脾DCs在体外直接对MHV-JHM感染敏感。成熟DCs的这种优先感染可能会抑制对该病毒的有效免疫反应的发展。
