日本脑炎病毒（JEV）是一种蚊子传播的黄病毒，由它导致的传染病我们称之为乙型脑炎，我国是这种传染病的高发国家之一。但是，仅有很小一部分JEV 感染的个人会引起症状，发展成严重的脑炎。由此可见，由于宿主本身的不同，引致了其对JEV的不同易感性。其感染后的临床疾病症状各异，包括非特异性发热，脑炎，甚至死亡，其中每250例感染患者中有1例会导致最终死亡。为何人群中对日本脑炎病毒具有不同的易感性的原因尚未可知。在感染病患中的低病毒血症为在JEV感染初期的诊断带来了困难。
实验室小鼠感染日本脑炎病毒后所产生的临床症状与人相似，因而其被用于研究日本脑炎病毒。中科院上海巴斯德研究所王恺博士在杜文圣（Vincent Deubel）研究员的指导下，通过对不同品系小鼠体内感染JEV的深入研究发现，这些小鼠体内并未有明显的病毒或宿主天然免疫标记，以区分高/低易感性小鼠。然而，在低易感性小鼠（DBA/2）中，可以引发更早更高水平的中和性抗体，可能一定程度上阻止了JEV入侵大脑。另外，在骨髓来源地巨噬细胞及树突状细胞上也呈现了更低的JEV感染率。提示这些差异可能是导致部分保护低易感性小鼠免遭JEV入侵神经的一种生物学因素。
该研究结果发表在PLoS ONE（2011;6(9):e24744）杂志上。本课题研究得到了上海巴斯德健康研究基金会的资助。(生物谷 Bioon.com)
doi:10.1371/journal.pone.0024744
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Mice with Different Susceptibility to Japanese Encephalitis Virus Infection Show Selective Neutralizing Antibody Response and Myeloid Cell Infectivity
Kai Wang, Vincent Deubel
Background
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes public health problems in Asian countries. Only a limited number of JEV-infected individuals show symptoms and develop severe encephalitis, indicating host-dependent susceptibilities.
Methodology/Principal Findings
C3H/HeN and DBA/2 mice, which exhibit different mortalities when infected by intraperitoneal inoculation with JEV, were used as experimental models to compare viral pathogenesis and host responses. One hundred infectious virus particles killed 95% of C3H/HeN mice whereas only 40% of DBA/2 mice died. JEV RNA was detected with similar low levels in peripheral lymphoid organs and in the sera of both mouse strains. High levels of viral and cytokine RNA were observed simultaneously in the brains of C3H/HeN and DBA/2 mice starting on days 6 and 9 post-infection, respectively. The kinetics of the cytokines in sera correlated with the viral replication in the brain. Significantly earlier and higher titers of neutralizing antibodies were detected in the DBA/2 strain. Primary embryonic fibroblasts, bone marrow-derived dendritic cells and macrophages from the two mouse strains were cultured. Fibroblasts displayed similar JEV replication abilities, whereas DBA/2-derived myeloid antigen-presenting cells had lower viral infectivity and production compared to the C3H/HeN–derived cells.
Conclusions/Significance
Mice with different susceptibilities to JEV neuroinvasion did not show changes in viral tropism and host innate immune responses prior to viral entry into the central nervous system. However, early and high neutralizing antibody responses may be crucial for preventing viral neuroinvasion and host fatality. In addition, low permissiveness of myeloid dendritic cells and macrophages to JEV infection in vitro may be elements associated with late and decreased mouse neuroinvasion.
