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Cited by 207Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Role of free radicals in viral pathogenesis and mutation

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Akaike, Takaaki·2001·Reviews in Medical Virology
DOI 10.1002/rmv.303PMC PMC7169086
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Abstract

Oxygen radicals and nitric oxide (NO) are generated in excess in a diverse array of microbial infections. Emerging concepts in free radical biology are now shedding light on the pathogenesis of various diseases. Free-radical induced pathogenicity in virus infections is of great importance, because evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. Although oxygen radicals and NO have an antimicrobial effect on bacteria and protozoa, they have opposing effects in virus infections such as influenza virus pneumonia and several other neurotropic virus infections. A high output of NO from inducible NO synthase, occurring in a variety of virus infections, produces highly reactive nitrogen oxide species, such as peroxynitrite, via interaction with oxygen radicals and reactive oxygen intermediates. The production of these various reactive species confers the diverse biological functions of NO. The reactive nitrogen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules. The unique biological properties of free radicals are further illustrated by recent evidence showing accelerated viral mutation by NO-induced oxidative stress. NO appears to affect a host's immune response, with immunopathological consequences. For example, NO is reported to suppress type 1 helper T cell-dependent immune responses during infections, leading to type 2 helper T cell-biased immunological host responses. NO-induced immunosuppression may thus contribute to the pathogenesis of virus infections and help expansion of quasispecies population of viral pathogens. This review describes the pathophysiological roles of free radicals in the pathogenesis of viral disease and in viral mutation as related to both nonspecific inflammatory responses and immunological host reactions modulated by NO.

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  • Vitamin C is an efficient water-soluble antioxidant and its effects on the immune system can be explained by protection against oxidative stress generated during infections.

    “Vitamin C is an efficient water‐soluble antioxidant and the effects on the immune system can be explained by the protection against oxidative stress generated during infections (Akaike 2001; Castro 2006; Hemilä 1992).”

    From Vitamin C for preventing and treating the common cold (2013) · cites this paper as Akaike 2001

    The sections on virus-induced oxidative stress and suppressive effects of NO on immunological responses say that viral infections generate oxidative stress and that it may suppress immune cells. They do not identify vitamin C as a water-soluble antioxidant or show that protection by vitamin C explains its effects on the immune system (searched: vitamin C, ascorbic acid). (LLM, conf=0.84)

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Research works printed but not linked: 8

  1. Stuehr DJ, Griffith OW. Mammalian nitric oxide synthase. Adv Enzymol Relat Areas Mol Biol 1992; 65: 287-346.
  2. Akaike T, Yoshida M, Miyamoto Y, et al. Antag- onistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/ e NO through a radical reaction. Biochemistry 1993; 32: 827-832.
  3. Oda T, Akaike T, Hamamoto T, et al. Oxygen Free radicals in virus infection 97 Copyright # 2001 John Wiley & Sons, Ltd. Rev. Med. Virol. 2001; 11: 87-101.
  4. Fridovich I. The biology of oxygen radicals. Science 1978; 201: 875-880.
  5. Rostasy K, Monti L, Yiannoutsos C, et al. Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activa- tion: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex. Ann Neurol 1999; 46: 207-216.
  6. Shiloh MU, Nathan CF. Reactive nitrogen inter- mediates and the pathogensis of Salmonella and mycobacteria. Curr Opin Microbiol 2000; 3: 35-42.
  7. Darrah PA, Hondalus MK, Chen Q, et al. Coopera- tion between reactive oxygen and nitrogen inter- mediates in killing of Rhodococcus equi by activated macrophages. Infect Immun 2000; 68: 3587-3593.
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Authors
Akaike, T.
Affiliations
Kumamoto University (JP)
Corresponding author
Akaike, Takaaki
ORCID
Akaike, Takaaki
Venue
Reviews in Medical Virology
Publisher
Wiley
Published
2001-03
Volume
11
Issue
2
Pages
87-101
ISSN
  • 1052-9276 (ISSN-L)
  • 1099-1654
DOI
10.1002/rmv.303
PMC
PMC7169086
OpenAlex
W2144466179
Cited by
207
References
142
Citations by year
2026: 2 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 17 · 2021: 16 · 2020: 17 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 3
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 15 d)
Locations
  • Reviews in Medical Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
free radicals, nitric oxide, superoxide, viral pathogenesis, viral mutations, oxidative stress, peroxynitrite, inducible nitric oxide synthase, reactive oxygen species, nitration, immunosuppression, Th1 cells, Th2 cells, quasispecies, influenza virus pneumonia, neurotropic viruses, oxidative tissue injury
MeSH terms
Animals, Humans, Mutation, Nitric Oxide, Superoxides, Virus Diseases, Viruses, Mice

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