THE OUTCOME OF POLIOVIRUS INFECTIONS IN K562 CELLS IS CYTOLYTIC RATHER THAN PERSISTENT AFTER HEMIN-INDUCED DIFFERENTIATION

K562-Mu erythroleukemia cells readily establish a long-term persistent poliovirus infection characterized by continuous virus production in the absence of complete p220 cleavage and host translation shutoff (R. E. Lloyd and M. Bovee, Virology 194:200-209, 1993). The mechanism of resistance appears to be modulated at the intracellular level and to b e related to decreased virus-mediated cytopathic effects (P. A. Benton , J. W. Murphy, and R. E. Lloyd Virology 213:7-18, 1995). It is well d ocumented that hemin induces the differentiation of K562 cells and alt ers the expression of several host proteins. We report here that growt h of K562 cells in hemin prior to poliovirus infection results in a do se-dependent increase in virus-induced cell lysis and thereby alters t he normally persistent outcome of infection to a more lytic phenotype. K562 cells infected after hemin treatment displayed increased host tr anslation shutoff, p220 cleavage, viral protein synthesis, and viral R NA accumulation compared with nontreated cells. Since hemin treatment of K562 cells also induced the increased expression of several heat sh ock proteins (Hsp70, Hsc70, Hsp90, and cohort p60), we tested the hypo thesis that their increased expression may play a role in altering pol iovirus infection in hemin-treated K562 cells. However, neither heat s tress nor oxidative stress, inducers of heat shock protein synthesis, altered the outcome of virus infections. In addition, we report the no vel finding that subunits of two translation initiation factors, p220 (eIF-4G) and eIF-2 alpha, are cleaved as a result of hemin treatment o f K562 cells. It is proposed that hemin alters the expression of speci fic host proteins in K562 cells, probably other than heat shock protei ns, which changes the initial response to poliovirus infections from p ersistent to lytic.