Aurothiolates enhance the replication of Semliki Forest virus in the CNS and the exocrine pancreas

The A7(74) strain of Semliki Forest virus (SFV) is avirulent and the L10 st rain virulent in adult mice. A7(74) infection of adult mouse brain gives ri se to small discrete foci of infection which, in immunocompetent animals, a re cleared within 10 days. In contrast L10 infection results in a widesprea d and fatal central nervous system infection. Aurothiolates are linear, 2-c oordinate complexes in which two ligands are covalently bound on either sid e of a gold nucleus in a +1 oxidation state (gold (I)). Pretreatment of A7( 74) infected mice with two distinct aurothiolates (sodium aurothiomalate an d aurothioglucose) resulted in significantly increased brain virus titers, and large confluent areas of infection in the brain similar to the pattern of infection seen with the L10 strain. The gold (I) moiety of aurothiolates was demonstrated to be the active component, since thiomalic acid when adm inistered alone had no potentiating effect on the infection. Although both aurothiolates allowed productive replication and spread of A7(74) within th e nature mouse brain, enhanced neuronal destruction was not apparent. There were no significant changes in virus distribution in any other tissue exce pt for the exocrine pancreas and the myocardium where widespread infection of the acinar cells and occasional infected myocytes were observed.