Long-term effect of elevated temperatures on SSPE virus expression in persistently infected rat glial cells

Cultivation of measles virus (SSPE virus, Lec strain) persistently infected C6 rat glioma cells at 39 degrees C resulted in the loss of detectable expression of measles virus proteins. Temperature shift-back led to reactivation of measles virus even after maintenance of the cells at 39 degrees C for 15 days. In Northern blot analysis viral mRNA disappeared at 3 days after shift-up whereas 50 S viral genome-sized RNA was detectable until 6 days. The 50 S RNA decreased in quantity in rough correlation with dilution by cell passage at 39 degrees C. The 50 S viral RNA was found in the nucleocapsid fraction. On day 9 after shift-down of persistently infected cells, maintained at 39 degrees C for 15 days, 50 S viral RNA reappeared although mRNAs were not yet detected. Infectious center assays showed that the number of cells in the population at 39 degrees C, which contained an SSPE virus genome that could be reactivated, declined after temperature shift. Moreover, cell cloning experiments, in which single cells of cultures maintained for various lengths of time at 39 degrees C were incubated at 35 degrees C and examined by immunofluorescence, reconfirmed the above results. This indicates that the reactivation of SSPE virus described here was due to re-infection of virus-antigen negative cells with progeny virus produced by a few latently infected cells in the population. The biological significance of this phenomenon in the central nervous system virus infection is discussed.