INTERFERON-ALPHA INHIBITS THE EMERGENCE OF CELLULAR STRESS RESPONSE-DEPENDENT MORBILLIVIRUS LARGE PLAQUE VARIANTS

Cellular levels of heat shock proteins (HSPs) are elevated in response to physiologic states accompanying acute virus infection (e.g. fever) . The objective of the present work was to define the antiviral effect of purified human lymphoblastoid IFN in the presence of HSP over-expr ession. For this purpose, canine distemper virus (CDV) was used since the response of CDV transcription and persistent infection phenotype t o elevated HSP is characterized. First, the effect of elevated HSP on CDV lytic infection phenotype in Vero and CV1 cells was defined, and r esults extended to the closely related measles virus (MV). Cells expre ssing elevated levels of the major inducible 70-kDa HSP (hsp72) suppor ted the emergence of large plaque variants of both CDV and MV from sma ll plaque purified inocula. IFN treatment concurrent with infection ca used a dosage-dependent reduction in the expression of large plaque va riants without affecting hsp72 levels or total plaque number. In contr ast to the stress response-induced large plaque variant, small plaques were resistant to the antiviral effects of IFN. These data demonstrat e the ability of IFN to selectively abrogate the pro-viral effects of HSP over-expression, inhibiting the formation of a plaque phenotype th at is correlated to enhanced virulence in animal models of morbillivir us encephalitis. (C) 1998 Elsevier Science B.V. All rights reserved.