Protective immunity, but suppressed immune responses to third party antigens are generated in cotton rats during measles virus infection

Abstract

Infection with measles virus leads to prolonged imune suppression in humans which is correlated with disease complications and secondary infections. Imune suppression is evidenced ex vivo by reduced proliferation towards mitogens and delayed hypersensitivity responses. The extent of inhibition of mitogen induced proliferation varies between 80 and 20% (for review see [l]). Inbred cotton rats are the only small animal model for intranasal infection with measles virus [21. Viral titers recovered from lung tissue after intranasal infection are directly correlated with the extent of proliferation inhibition. Viral titers peak on day 4 to 5 and immune suppression is most marked on day 4 (70%). On day ten neither viable virus nor immune suppression is observed. The minimal immunsuppressive dose is lo6 plaque forming units (pfu) and the minimal infectious dose 5x103 pfu. We have tested various Band Tcell mitogens (Viticia sativa, Phytolacca americana, Pokeweed mitogen, Lipopolysaccharides and Concanavalin A) in this proliferation assay. Proliferation inhibition was independent of the lymphocyte subset stimulated. Immune suppression is also seen in a mixed lymphocyte reaction and cannot simply be reverted by supplementation of IL2. In vivo, the induction of a primary as well as a secondary immune response towards normal horse serum is reduced after intranasal measles virus infection. However, infection does not affect antigen specific cells as long as they are not activated during infection. In contrast to this inhibitory effect, the measles virus specific immune response which is generated one week after infection protects against reinfection. To define the protein specificity of the protective immune response, we have infected cotton rats one week after intranasal infection with measles virus with vaccinia virus recombinants expressing single measles virus proteins [ 3 ] , [4]. Animals were protected against infection with recombinant vaccinia viruses expressing the nucleoprotein, hemagglutinin and fusion protein but not irrelevant control proteins. In s m a r y , in cotton rats measles virus infection induces a good protective immune response. At the same time responses towards third party antigen are reduced. It seems that cotton rats are a good animal model to study measles virus immune suppression.