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Production of High-Titer Recombinant Newcastle Disease Virus from Allantoic Fluid
Published on: May 25, 2022
Cell-type-specific innate immune response to oncolytic Newcastle disease virus
Moanaro Biswas1, Sandeep R P Kumar, Adria Allen
1Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Abstract:
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.
Insights
Newcastle disease virus (NDV) shows promise for cancer virotherapy by selectively targeting tumor cells. Its tumor selectivity is linked to the retinoic acid-inducible gene I (RIG-I) pathway and cellular antiviral responses.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Virotherapy utilizes oncolytic viruses for cancer treatment, selectively targeting tumor cells.
- Newcastle disease virus (NDV) is an oncolytic virus whose tumor selectivity depends on the type I interferon (IFN) response.
- Understanding NDV's mechanisms and immune interactions is crucial for enhancing its oncolytic potential.
Purpose of the Study:
- To investigate the infection kinetics and innate immune responses to a recombinant NDV (rLaSota eGFP) in human tumor and normal cells.
- To elucidate the role of cellular antiviral pathways, specifically RIG-I, in NDV's tumor selectivity.
- To analyze the differential expression of cytokines and chemokines in response to NDV infection in various cell types.
Main Methods:
- Infection of human tumor and normal cell lines with recombinant LaSota strain of NDV expressing eGFP (rLaSota eGFP).
- Assessment of viral replication, cytotoxicity, and innate immune responses, including type I IFN and cytokine/chemokine profiles.
- Evaluation of the role of retinoic acid-inducible gene I (RIG-I) in cellular sensitivity to NDV.
Main Results:
- rLaSota eGFP exhibited variable replication and cytotoxicity across different tumor cell types, with restricted replication in normal cells.
- Absence of RIG-I was identified as a key factor determining sensitivity to NDV infection.
- Human multiple myeloma cells showed productive NDV infection with moderate IFN-α induction, suggesting potential IFN-independent mechanisms or impaired RIG-I function.
- Differential alterations in proinflammatory cytokines and chemokines were observed in infected normal versus tumor cells.
Conclusions:
- Tumor selectivity of NDV is influenced by variations in the cellular antiviral response, particularly RIG-I expression.
- RIG-I plays a critical role in mediating cellular sensitivity and response to NDV infection.
- Further research into NDV-host interactions can optimize its application in cancer virotherapy.
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