Cell-type-specific innate immune response to oncolytic Newcastle disease virus.
Virotherapy of cancer exploits the potential of naturally occurring and engineered oncolytic viruses to selectively replicate in and cause cytotoxicity to tumor cells without affecting healthy normal cells. The tumor selectivity of Newcastle disease virus (NDV), a member of the family Paramyxoviridae, depends on the differential type I interferon (IFN) response. Further understanding of the key mechanisms and immune effector molecules involved will aid in augmenting the oncolytic properties of NDV. Here we report on the infection kinetics and innate immune responses to a recombinant LaSota strain of NDV (rLaSota eGFP) in human tumor and normal cells. We observed varying replicative fit and cytotoxicity of rLaSota eGFP depending on the tumor cell type, with severely restricted replication in normal cells. The absence of retinoic acid-inducible gene I (RIG-I), a cytosolic RNA sensor, determined sensitivity to NDV. Productive NDV infection with a moderate IFN-α induction in human multiple myeloma cells suggested a role for IFN-independent mechanisms or lack of type I IFN reinforcement by RIG-I. Proinflammatory cytokines and chemokines were altered differentially in infected normal and tumor cells. Our results suggest that tumor selectivity is dependent on variations in the cellular antiviral response to infection with NDV and RIG-I expression.
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Moanaro
M
Biswas
Sandeep R P
SR
Kumar
Adria
A
Allen
Wang
W
Yong
Ramadevi
R
Nimmanapalli
Siba K
SK
Samal
Subbiah
S
Elankumaran
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011971:Receptors, Immunologic; D014709:Vero Cells; D014779:Virus Replication
D000998:Antiviral Agents; D007370:Interferon Type I; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases