Coevolution of virulent virus and resistant cells as a mechanism of persistence of herpes simplex virus type 1 in a human T lymphoblastoid cell line.
Infection of the lymphoblastoid CEM cell line with herpes simplex virus (HSV) type 1 results in a persistent infection with production of infectious virus. Evidence suggests that the persistent infection was not maintained by interferon or non-interferon-soluble antiviral inhibitors. Treatment of persistently infected cells with anti-HSV serum (termed CEMACR cells) or elevated temperature (39 degrees C) for 14 days (termed CEMTCR cells) resulted in loss of evidence of virus. HSV DNA was not detected in CEMACR or CEMTCR cells by Southern blot or in situ hybridization. The CEMACR or CEMTCR cells, however, were resistant to reinfection with homologous, parental virus (HSV0), but were susceptible to heterologous virus (vesicular stomatitis virus). Resistance to reinfection with HSV was not absolute; CEMACR or CEMTCR cells were less permissive to virus isolated from persistently infected cultures at times early in the course of infection, but were more permissive for HSV isolated at later times. Virus isolated later during persistent infection also displayed progressively increased virulence for the parental CEM cells. These results suggest that persistent infection of a human T lymphoblastoid cell line, CEM, with HSV-1 is maintained by a genetically determined cell-virus equilibrium, in which the resistance of cells and virulence of virus increase during persistence.
Cummings
P J
PJ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania.
Rinaldo
C R
CR
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D009693:Nucleic Acid Hybridization; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D013601:T-Lymphocytes / Q000382:microbiology*; D013696:Temperature; D014709:Vero Cells; D014774:Virulence; D014779:Virus Replication
D004279:DNA, Viral; D004247:DNA