New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.
BACKGROUND
Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.


RESULTS
We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs.


CONCLUSIONS
Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility for virus propagation.
Prescott
Joseph
J
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
Hall
Pamela
P
Acuna-Retamar
Mariana
M
Ye
Chunyan
C
Wathelet
Marc G
MG
Ebihara
Hideki
H
Feldmann
Heinz
H
Hjelle
Brian
B
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006476:Orthohantavirus / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D007372:Interferons / Q000096:biosynthesis* / Q000378:metabolism; D014709:Vero Cells; D014779:Virus Replication
D007370:Interferon Type I; D007372:Interferons