Smith A L, de Souza M S, Finzi D, Barthold S W
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Arch Virol. 1992;125(1-4):39-52. doi: 10.1007/BF01309627.
Oral and/or intranasal inoculation of susceptible mouse genotypes with the JHM strain of mouse hepatitis virus (MHV-JHM) consistently results in T cell dysfunction as reflected by in vitro proliferative responses to mitogens or allogeneic cells. One approach to examining the mechanism responsible for the observed functional T cell suppression is to determine whether virus replication is required for its induction. To this end, mice were inoculated oronasally with MHV-JHM that was inactivated with short-wave ultraviolet light, beta-propiolactone or psoralen. Mice were also inoculated with live MHV-JHM after recovery from homotypic or heterotypic MHV infection. Spleen cells from BALB mice inoculated oronasally with inactivated MHV-JHM yielded extremely variable in vitro proliferative responses after concanavalin A stimulation. MHV-susceptible mice exposed oronasally or intraperitoneally to virus inactivated by any of the minimum effective treatments failed to seroconvert. Immunization with psoralen-treated virus intraperitoneally in Freund's complete adjuvant or oronasally failed to protect from live virus challenge, but survivors had elevated virus-specific serum IgG antibody titers compared to mock-immunized controls at two weeks post-challenge. Spleen cells from mice that were challenged after recovery from homotypic live virus infection did not exhibit the profound in vitro T cell suppression normally observed during the acute stage of primary infection. In contrast, MHV-JHM challenge of mice vaccinated with heterotypic live MHV-S resulted in significantly depressed in vitro T cell function. The combined data suggest that either virus replication or exposure to more concentrated antigen may be required for induction of the dramatic T cell dysfunction that occurs as a consequence of MHV-JHM infection as well as for a detectable MHV-specific humoral response.
用小鼠肝炎病毒JHM株（MHV-JHM）经口和/或鼻内接种易感小鼠基因型，始终会导致T细胞功能障碍，这可通过对有丝分裂原或同种异体细胞的体外增殖反应来反映。研究导致所观察到的功能性T细胞抑制机制的一种方法是确定其诱导是否需要病毒复制。为此，用短波紫外线、β-丙内酯或补骨脂素灭活的MHV-JHM经口接种小鼠。从同型或异型MHV感染恢复后，小鼠也接种活的MHV-JHM。经口接种灭活的MHV-JHM的BALB小鼠的脾细胞在伴刀豆球蛋白A刺激后产生的体外增殖反应变化极大。经口或腹腔暴露于任何一种最低有效处理灭活的病毒的MHV易感小鼠未能发生血清转化。在弗氏完全佐剂中经腹腔或经口用补骨脂素处理的病毒免疫未能保护小鼠免受活病毒攻击，但与假免疫对照相比，存活小鼠在攻击后两周时病毒特异性血清IgG抗体滴度升高。从同型活病毒感染恢复后受到攻击的小鼠的脾细胞未表现出在原发性感染急性期通常观察到的确切的体外T细胞抑制。相反，用异型活MHV-S疫苗接种的小鼠接受MHV-JHM攻击导致体外T细胞功能明显受抑。综合数据表明，诱导因MHV-JHM感染而发生的显著T细胞功能障碍以及可检测到的MHV特异性体液反应可能需要病毒复制或暴露于更浓缩的抗原。
