日本腦炎病毒（JEV）是一種蚊子傳播的黃病毒,，由它導(dǎo)致的傳染病我們稱之為乙型腦炎,，我國是這種傳染病的高發(fā)國家之一。但是,，僅有很小一部分JEV 感染的個(gè)人會(huì)引起癥狀,，發(fā)展成嚴(yán)重的腦炎。由此可見,，由于宿主本身的不同,，引致了其對JEV的不同易感性。其感染后的臨床疾病癥狀各異,，包括非特異性發(fā)熱,，腦炎，甚至死亡,，其中每250例感染患者中有1例會(huì)導(dǎo)致最終死亡,。為何人群中對日本腦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癥為在JEV感染初期的診斷帶來了困難,。
實(shí)驗(yàn)室小鼠感染日本腦炎病毒后所產(chǎn)生的臨床癥狀與人相似,，因而其被用于研究日本腦炎病毒。中科院上海巴斯德研究所王愷博士在杜文圣（Vincent Deubel）研究員的指導(dǎo)下,，通過對不同品系小鼠體內(nèi)感染JEV的深入研究發(fā)現(xiàn),，這些小鼠體內(nèi)并未有明顯的病毒或宿主天然免疫標(biāo)記，以區(qū)分高/低易感性小鼠,。然而,，在低易感性小鼠（DBA/2）中，可以引發(fā)更早更高水平的中和性抗體,，可能一定程度上阻止了JEV入侵大腦,。另外,，在骨髓來源地巨噬細(xì)胞及樹突狀細(xì)胞上也呈現(xiàn)了更低的JEV感染率。提示這些差異可能是導(dǎo)致部分保護(hù)低易感性小鼠免遭JEV入侵神經(jīng)的一種生物學(xué)因素,。
該研究結(jié)果發(fā)表在PLoS ONE（2011;6(9):e24744）雜志上,。本課題研究得到了上海巴斯德健康研究基金會(huì)的資助。(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.
