Reversible repression and activation of measles virus infection in neural cells.
Conversion of acute measles virus infection to an indolent state has been achieved by treatment of infected cells of neural origin with agents that affect cyclic nucleotide metabolism. Striking results were obtained with papaverine, an inhibitor of cAMP phosphodiesterase that is capable of enhancing neural differentiation. In papaverine-treated cultures, decreased production of infectious virus was accompanied by selective disappearance of intracellular matrix proton, as detected by immunofluorescence. Viral nucleocapsid protein was enhanced in the cytoplasm while three other structural proteins--polymerase, hemagglutinin, and fusion protein--showed little change in distribution or intensity of staining. These results were specific for cells of neural origin and not observed in CV-1 or Vero cultures. cAMP, dibutyryl cAMP, 8-bromo-cAMP, and isobutylmethylxanthine all inhibited replication of virus but less so than did papaverine. Inhibition of virus replication by any of these agents was rapidly reversible, either by removal of the agent or by addition of cGMP to the culture medium and was accompanied by reappearance of the matrix protein. These results suggest that measles virus replication in neural cells depends on host factors, particularly those affecting endogenous cAMP and cGMP. Viral persistence may thus be related to the state of neural differentiation. This model system may yield information on mechanisms of recrudescence observed in some chronic diseases of the nervous system.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D008457:Measles / Q000382:microbiology*; D008459:Measles virus / Q000254:growth & development* / Q000276:immunology; D051379:Mice; D009474:Neurons / Q000382:microbiology*; D014779:Virus Replication
D000956:Antigens, Viral; D000242:Cyclic AMP