Mice lacking inducible nitric-oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses.

Division of Virology, University of Glasgow, UK.
Journal of General Virology (Impact Factor: 3.13). 05/1998; 79 ( Pt 4):825-30.
Source: PubMed

ABSTRACT Mice deficient in the inducible nitric-oxide synthase (iNOS), constructed by gene-targeting, were significantly more susceptible to herpes simplex virus (HSV)-1 infection, displayed a delayed clearance of virus from the dorsal root ganglia (DRG) and exhibited an increase in the frequency of virus reactivation in DRG compared with similarly infected heterozygous mice. The infected iNOS-deficient mice developed enhanced Th1-type immune responses and their spleen cells produced higher concentrations of IL-12 than similarly infected heterozygous mice. This finding suggests that iNOS plays an important role in resistance against HSV-1 infection. Furthermore, nitric oxide (NO) may block the development of Th1 cells via inhibition of IL-12 synthesis and thereby play a role in immune regulation.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advances in free radical research show that reactive oxygen and nitrogen oxide species, for example superoxide, nitric oxide (NO) and peroxynitrite, play an important role in the pathogenesis of different viral infections, including dengue virus. The pathogenic mechanism of dengue haemorrhagic fever (DHF) is complicated and is not clearly understood. The hallmarks of the dengue disease, the antibody-dependent enhancement, the shift from T-helper type 1 (Th1) to Th2 cytokine response and the cytokine tsunami resulting in vascular leakage can now be explained much better with the knowledge gained about NO and peroxynitrite. This paper makes an effort to present a synthesis of the current opinions to explain the pathogenesis of DHF/shock syndrome with NO on centre stage.
    FEMS Immunology & Medical Microbiology 03/2009; 56(1):9-24. · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: WHEN AN ANTIVIRAL IMMUNE RESPONSE IS GENERATED, A BALANCE MUST BE REACHED BETWEEN TWO OPPOSING PATHWAYS: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.
    Frontiers in Immunology 09/2014; 5:428.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The incidence of skin and soft tissue infections (SSTI) due to multi-drug resistant pathogens is increasing. The concomitant increase in antibiotic use along with the ease with which organisms develop mechanisms of resistance have together become a medical crisis, underscoring the importance of developing innovative and effective antimicrobial strategies. Nitric oxide (NO) is an endogenously produced molecule with many physiologic functions, including broad spectrum antimicrobial activity and immunomodulatory properties. The risk of resistance to NO is minimized because NO has multiple mechanisms of antimicrobial action. NO's clinical utility has been limited largely because it is highly reactive and lacks appropriate vehicles for storage and delivery. To harness NO's antimicrobial potential, a variety exogenous NO delivery platforms have been developed and evaluated, yet limitations preclude their use in the clinical setting. Nanotechnology represents a paradigm through which these limitations can be overcome, allowing for the encapsulation, controlled release, and focused delivery of NO for the treatment of SSTI. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1230 For further resources related to this article, please visit the WIREs website.
    Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 05/2013; · 5.68 Impact Factor

Full-text (2 Sources)

Available from
May 16, 2014