The significance and nature of defective interfering viruses

Abstract

Deletions in viral genomes appear to be a common occurrence in the replication of all DNA and RNA viruses which have been adequately studied. Such defective genomes can replicate in the presence in the same cell of a helper virus as long as the deletion does not involve the initiation site for genome replication. Coinfection of a cell with defective and "normal" infectious virus leads to reduction in the yield of the latter. The nature of DI viruses and genomes found in Sindbis virus-infected vertebrate cells during "undiluted passage" series is discussed. This procedure leads to the accumulation of progressively shorter viral RNA genomes with internal deletions. The enrichment is limited to genome lengths which are integral fractions (1/2, 1/3, 1/4, etc.) of the complete genome, and these are also found in viral particles released at the corresponding passage levels. It is believed that the selective accumulation of these fragments is governed by constraints of assembly which demand that one full genome equivalent be packaged in a released particle. In contrast to vertebrate cells, cultured mosquito cells do not seem to produce or "recognize" DI particles. Possible implications for the epidemiology of arthropod-transmitted alphaviruses are presented.