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Role of nitric oxide in immune responses against viruses: beyond microbicidal activity

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Abstract

Introduction

Nitric oxide (NO) is a free radical produced during l-arginine metabolism. In addition to its physiological activities in vascular and neuronal functions, its role in the immune system as a microbicide and tumor-killing mediator has been well described, as well as its release by activated macrophages. Furthermore, NO is produced by a variety of immune and non-immune cells and is involved in the regulation of several immune functions, such as T-cell polarization and suppression.

Results

Viral infections generally promote NO production; however, according to its concentration, NO can trigger different effector mechanisms in immune responses. NO can activate the second messenger cyclic guanosine monophosphate (cGMP), can increase the cytoplasmic p53 tumor suppressor molecule, and can modify host and viral molecules by nitrosylation. Because of its microbicide function, NO has frequently been considered a protective mediator in viral infections; however, in some cases NO could be deleterious, potentiating inflammation or contributing to virus latency.

Conclusions

Thus, advances in the knowledge of the role of NO in immunomodulation and in the pathogenesis of viral diseases could contribute not only to the development of vaccines and therapeutic strategies but also to the use of its metabolites (nitrate/nitrite) and the enzyme responsible for its production (iNOS) as prognostic markers of some of these viral infections.

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Abbreviations

DAMP:

Danger-associated molecular pattern

d-NMA:

N G-methyl-d-arginine

iNOS:

Inducible nitric oxide synthase

IRF1:

Interferon regulatory factor 1

l-NMA:

N G-Methyl-l-arginine

l-NMMA:

N G-Monomethyl-l-arginine

PAMP:

Pathogen-associated molecular pattern

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Acknowledgments

We would like to thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP—2013/03563-6) for funding support.

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Authors and Affiliations

  1. Immunology Center, Adolfo Lutz Institute, Av. Dr. Arnaldo, 351, 10º andar, São Paulo, 01246-902, Brazil

    Elaine Uchima Uehara, Beatriz de Stefano Shida & Cyro Alves de Brito

  2. Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

    Elaine Uchima Uehara

  3. Laboratory of Dermatology and Immunodeficiencies (LIM-56), Medical School of the University of São Paulo, São Paulo, Brazil

    Cyro Alves de Brito

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  1. Elaine Uchima Uehara
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Correspondence to Cyro Alves de Brito.

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Uehara, E.U., Shida, B.S. & de Brito, C.A. Role of nitric oxide in immune responses against viruses: beyond microbicidal activity. Inflamm. Res. 64, 845–852 (2015). https://doi.org/10.1007/s00011-015-0857-2

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