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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Apr 26;91(9):3705–3709. doi: 10.1073/pnas.91.9.3705

Rapid cell variation can determine the establishment of a persistent viral infection.

A M Martín Hernández 1, E C Carrillo 1, N Sevilla 1, E Domingo 1
PMCID: PMC43650  PMID: 8170973

Abstract

Evidence for a mechanism of initiation of viral persistence in which the cell, and not the virus, plays a critical role has been obtained using the important animal pathogen foot-and-mouth disease virus (FMDV). We have developed a virulence assay consisting of quantification of the ability of virus to kill cells and of cells to divide in the presence of virus and to initiate a carrier state. Cells were cured of FMDV at early times following a cytolytic infection of BHK-21 monolayers with FMDV. When cured cells were subjected to the virulence assay they showed an increased ability to survive a second infection by FMDV but not by other RNA viruses. This altered phenotype was maintained as a stable genetic trait. When the virus present in such early surviving cells was used to infect BHK-21 cells, it proved to be as virulent as the initial cytolytic FMDV and, furthermore, its ability to kill BHK-21 cells increased upon replication in the surviving cells. Both the level of genetic heterogeneity and the rate of evolution of FMDV were similar to those previously documented during acute and persistent FMDV infections. The results suggest that, in contrast to most other viral systems, the critical element in the establishment of a persistent infection of BHK-21 cells with FMDV is the ability of the host cells to vary genetically and phenotypically, which promotes selection of cells with increased resistance to virus. The possible relevance of this mechanism to viral persistence in vivo is discussed.

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Selected References

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