Responses of mice to murine coronavirus immunization.
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.
Smith
A L
AL
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
de Souza
M S
MS
Finzi
D
D
Barthold
S W
SW
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D005260:Female; D005363:Ficusin / Q000494:pharmacology; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D011420:Propiolactone / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014466:Ultraviolet Rays; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D014779:Virus Replication
D000956:Antigens, Viral; D014765:Viral Vaccines; D011420:Propiolactone; D005363:Ficusin