Molecular variation of type 1 vaccine-related and wild polioviruses during replication in humans

Abstract

Molecular variation in clinical isolates of type 1 poliovirus was followed at the level of the genome by oligonucleotide mapping and at the level of the gene products by polyacrylamide gel electrophoresis of the viral proteins. Oligonucleotide maps of epidemiologically distinct isolates were very different. In contrast, isolates from the recent Netherlands-Canada-USA poliomyelitis epidemic displayed very similar maps. Small but reproducible map changes were consistently observed for consecutive case isolates, which revealed the continual mutation and selection of the epidemic virus during replication in humans. Direct comparison of the maps of the first (Netherlands, 5/78) and the last (USA 6/79) epidemic case isolates suggested that about 100 base changes were fixed into the average viral genome during 13 months of epidemic transmission. Isolates from two recent vaccinees and one epidemiologically unrecognized contact similarly revealed small map differences from each other and from the pattern characteristic of the type 1 oral vaccine. Accompanying the genome changes were alterations in the mobilities and cleavage rates of the viral proteins. For both vaccine-related and wild isolates, the greatest variabilities were detected in the virion surface proteins, a pattern of change likely to lead to antigenic drift of the virus. Oligonucleotide mapping offers an independent and definitive approach for the recognition of genetic and epidemiologic relationships between poliovirus isolates.