Virulence heterogeneity of a predominantly avirulent Western equine encephalitis virus population

Selective removal of small plaque (SP) Western equine encephalitis (WEE) virus from a population heterogeneous with respect to virulence and plaque morphology permitted direct detection of a small sub-population of virulent large plaque (LP) WEE virus. Selective removal of SP-WEE virus was achieved by intracardiac (i.c.a.) inoculation of hamsters; plasma obtained 60 min after inoculation was proportionately enriched for LP-WEE virus since only the SP-WEE virus was cleared. By this method, the proportion of LP- to SP-WEE virus, in a population of SP-WEE virus which appeared to be homogeneous by conventional plaquing methods, was calculated to be 1 LP- to 250000 SP-WEE virions. The presence of a virulent LP-WEE virus sub-population explains why a single passage of a high but not low dose of SP-WEE virus in hamsters resulted in the emergence of an LP-WEE virus population with enhanced virulence.