K562 CELL STRAINS DIFFER IN THEIR RESPONSE TO POLIOVIRUS INFECTION

Poliovirus readily establishes a persistent infection in the K562-Mu e rythroleukemia cell strain. In this study, three additional K562 cell strains were analyzed for their responses to poliovirus infection and found to be quite variable. K562 cells obtained from the ATCC establis hed a persistent infection, similar to the K562-Mu cell strain, while the majority of cells from two other strains, K562-Kl and K562-We, wer e killed by 4 or 11 days postinfection (p.i.), respectively. Several c haracteristics of the uninfected and infected cell strains were examin ed to determine if differences existed which could explain the dramati cally different responses to infection. Since K562 cell strains can di fferentiate toward several cell lineages, the four strains were analyz ed for physical and functional likeness to the original K562 cell line using well-established functional criteria to determine whether gross changes in differentiation state had occurred. Based on the lack of M HC class I antigen expression and a dose-dependent increase in globin synthesis in response to hemin, all three laboratory K562 cell strains were indistinguishable from the ATCC reference strain. Surface poliov irus receptor levels were also similar in all K562 cell strains, altho ugh four- to fivefold lower than those in HeLa cells. Most biochemical events in virus replication either were very similar among K562 cells or were slightly variable and did not correlate with the degree of ce ll killing. These included levels of virus production, levels of viral protein produced, and processing and turnover of viral polypeptides. The key difference between the cell strains which consistently correla ted with cell killing was the degree of virus-induced host translation shutoff, which was always greatest in the most virus-sensitive K562-K I cells. In addition, levels of 2A(pro) produced in K562 cell strains did not appear to correlate with the levels of host protein shutoff. A related and novel finding in these studies which also strongly correl ated with the outcome of infection was the ability of levels of intact p220 to recover by 24 hr p.i. in virus-resistant K562-Mu and -ATCC ce lls. These data suggest that the key determinants of outcome of infect ion in this cell model are cytoplasmic host factors related to cytopat hology and not factors which may modulate levels of viral protein synt hesis or RNA synthesis. (C) 1995 Academic Press, Inc.