COLD STRESS-INDUCED NEUROINVASIVENESS OF ATTENUATED ARBOVIRUSES IS NOT SOLELY MEDIATED BY CORTICOSTERONE

In previous studies we have shown that various stress paradigms can in duce the penetration of noninvasive, attenuated viruses into the centr al nervous system (CNS). Since glucocorticoids levels are elevated dur ing stress, we compared the effect of cold stress and corticosterone ( CS) injection on neuroinvasiveness of a non-invasive encephalitic viru s, WN-25 (West Nile). Exposure of inoculated mice to cold stress or CS resulted in high viremia and a marked increase in mortality when comp ared to control untreated mice. Exposure of WN-25 inoculated mice to c old treatment or CS injection led to high blood virus levels as compar ed to nontreated mice (3.2 and 3.1 vs. > 1 log 10 PFU/ml). Cold stress or CS (5 000 ng/mouse) treatment caused a mortality rate of 70% and 5 0% of the WN-25 inoculated mice respectively. No mortality was recorde d in control inoculated groups (p < 0.05). Passive transfer serum from uninfected cold stressed mice to WN-25 inoculated nonstressed mice, r esulted in similar mortality. The levels of CS in passive transferred serum from cold stressed animals was 500 ng/ml, only 2% (100 vs. 5 000 ng) of the CS dose required to obtain a similar effect on viral penet ration and mortality when CS was injected directly. Therefore, we conc luded that CS was not the sole factor responsible for the cold stress effect on the viral infection outcome.