SINDBIS VIRUS-INFECTION OF NEONATAL MICE RESULTS IN A SEVERE STRESS-RESPONSE

Neonatal mice were infected with virus derived from a molecular clone of a laboratory strain of Sindbis virus, TRSB. The resulting acute fat al infection was typified by few if any of the classic hallmarks of en cephalitis, very high levels of interferon-alpha/beta (IFN alpha beta) , and lesions in the thymus and hematopoietic tissues usually associat ed with a severe stress response. infection with an attenuated mutant of TRSB, which harbors a single amino acid change in the E2 surface gl ycoprotein (TRSBr114), was characterized by encephalitis, reduced mort ality, low levels of IFN alpha beta, and no thymic pathology (J. Trgov cich, J. F. Aronson, and R. E. Johnston, 1996, Virology 224, 73-83). H ere we report that infection of neonatal mice with TRSB, but not TRSBr 114, resulted in induction of high levers of tumor necrosis factor-alp ha as well as high and sustained levels of adrenalcorticotropin-releas ing hormone and corticosterone. This syndrome of potentially toxic cyt okine and stress hormone induction correlates with lethal Sindbis viru s infection and constitutes a previously unrecognized aspect of Sindbi s virus pathogenesis in mice. (C) 1997 Academic Press