Archives of Virology

, Volume 161, Issue 8, pp 2075–2086 | Cite as

Activation of toll-like receptor signaling pathways leading to nitric oxide-mediated antiviral responses

  • Mohamed Sarjoon Abdul-Cader
  • Aruna Amarasinghe
  • Mohamed Faizal Abdul-CareemEmail author


Toll-like receptors (TLRs), well-characterized pattern-recognizing receptors of the innate arm of the immune system, are vital in detecting pathogen-associated molecular patterns (PAMPs). The TLR-PAMP interaction initiates an intracellular signaling cascade, predominantly culminating in upregulation of antiviral components, including inducible nitric oxide synthase (iNOS). After activation, various TLR pathways can promote iNOS production via the myeloid differentiation primary response-88 (MyD-88) adapter protein. Subsequently, iNOS facilitates production of nitric oxide (NO), a highly reactive and potent antiviral molecule that can inhibit replication of RNA and DNA viruses. Furthermore, NO can diffuse freely across cell membranes and elicit antiviral mechanisms in various ways, including direct and indirect damage to viral genomes. This review emphasizes current knowledge of NO-mediated antiviral responses elicited after activation of TLR signaling pathways.


Nitric Oxide Respiratory Syncytial Virus Influenza Virus Infection Infectious Bursal Disease Virus Antiviral Mechanism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The graduate programs of M.S.A and A.A. are supported by the Margaret Gunn Endowment for Animal Research (University of Calgary), Agriculture and Agri-Food Canada, and Saskatchewan Agriculture Ministry (Canada) grants received by MFA. We thank Dr. John Kastelic, University of Calgary Faculty of Veterinary Medicine, for extensive editing of the manuscript.

Compliance with ethical standards


Margaret Gunn Endowment for Animal Research, University of Calgary, Canada (10007898); Agriculture and Agri-Food Canada (10009962); Saskatchewan Agriculture Ministry, Canada (10010719).

Conflict of interest

Mohamed Sarjoon Abdul-Cader declares that he has no conflict of interest. Aruna Amarasinghe declares that he has no conflict of interest. Mohamed Faizal Abdul-Careem declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Mohamed Sarjoon Abdul-Cader
    • 1
  • Aruna Amarasinghe
    • 1
  • Mohamed Faizal Abdul-Careem
    • 1
    Email author
  1. 1.Department of Ecosystem and Public Health, Faculty of Veterinary MedicineUniversity of CalgaryCalgaryCanada

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