Virulent and nonvirulent forms of Plasmodium yoelii are not restricted to growth within a single erythrocyte type.

The present studies were designed to investigate whether the erythrocyte preferences displayed by both virulent and nonvirulent forms of Plasmodium yoelii were fastidious growth requirements of these parasites. When inoculated into mice depleted of reticulocytes by lethal irradiation (900 rad), virulent parasites, which have been reported to grow predominantly in mature erythrocytes, gave rise to high parasitemias which were equivalent to those seen in unirradiated, normal mice. In addition, virulent parasites serially passaged in lethally irradiated mice showed properties of enhanced virulence upon inoculation back into normal mice. When inoculated into lethally irradiated mice, nonvirulent P. yoelii, which were reported to preferentially invade reticulocytes, invaded mature erythrocytes, and the infection progressed at a higher level of parasitemia than in unirradiated, normal mice. The inoculation of virulent parasites into mice made reticulocytemic by pretreatment with phenylhydrazine produced infections marked by the invasion of reticulocytes rather than mature erythrocytes, yet these infections remained lethal for the murine host. When nonvirulent parasites were inoculated into reticulocytemic mice, lethal infections resulted in which the parasites predominantly invaded reticulocytes. These results indicate that both the virulent and nonvirulent forms of P. yoelii possess the ability to invade and proliferate within more than one erythrocyte type and that their apparent erythrocyte preferences are not strict growth requirements.