LCM VIRUS INDUCED ENDOCRINE DYSFUNCTION

The investigator proposes to apply the techniques of molecular biology to the investigation on the basis of the LCMV-induced repression of differentiated function in persistently infected cells. Two areas of examination are outlined in the proposal. The first addresses the question of whether the observed depression in growth hormone production in the pituitaries of persistently infected animals is a result of an alteration in the steady state level of growth hormone mRNA or is due to reduction in the translation of growth hormone mRNA. The second area of inquiry is to conduct an analysis of the viral RNA present in persistently infected tissues and cells in order to understand the mechanisms of viral persistence. Both approaches will utilize Northern blot hybridization of RNAs extracted from infected tissues or cells. The blots will be interrogated with nick translated probes prepared from a recombinant plasmid containing a partial rat growth hormone cDNA or with probes prepared from cloned L and S segments of viral nucleic acid. In addition, GH synthesis will be studied by analysis of polysomal mRNAs as well as in vitro translation of the infected cell poly (A)+ RNA.