Decreased virus population diversity in p53-null mice infected with weakly oncogenic Abelson virus.
The Abelson murine leukemia virus (Ab-MLV), like other retroviruses that contain v-onc genes, arose following a recombination event between a replicating retrovirus and a cellular oncogene. Although experimentally validated models have been presented to address the mechanism by which oncogene capture occurs, very little is known about the events that influence emerging viruses following the recombination event that incorporates the cellular sequences. One feature that may play a role is the genetic makeup of the host in which the virus arises; a number of host genes, including oncogenes and tumor suppressor genes, have been shown to affect the pathogenesis of many murine leukemia viruses. To examine how a host gene might affect an emerging v-onc gene-containing retrovirus, we studied the weakly oncogenic Ab-MLV-P90A strain, a mutant that generates highly oncogenic variants in vivo, and compared the viral populations in normal mice and mice lacking the p53 tumor suppressor gene. While variants arose in both p53+/+ and p53-/- tumors, the samples from the wild-type animals contained a more diverse virus population. Differences in virus population diversity were not observed when wild-type and null animals were infected with a highly oncogenic wild-type strain of Ab-MLV. These results indicate that p53, and presumably other host genes, affects the selective forces that operate on virus populations in vivo and likely influences the evolution of oncogenic retroviruses such as Ab-MLV.
Marchlik
Erica
E
Immunology Graduate Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Kalman
Richard
R
Rosenberg
Naomi
N
D000011:Abelson murine leukemia virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016158:Genes, p53; D014644:Genetic Variation; D007942:Leukemia, Experimental / Q000235:genetics* / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009154:Mutation; D012192:Retroviridae Infections / Q000235:genetics* / Q000821:virology*; D014412:Tumor Virus Infections / Q000235:genetics* / Q000821:virology*; D014774:Virulence / Q000235:genetics; D016662:Virus Integration / Q000235:genetics
D004279:DNA, Viral