viral infections, nitric oxide, oxidative stress

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1: Free Radic Biol Med. 1996;21(5):641-9.

*Oxidative stress during viral infection: a review.*

Schwarz KB.

Department of Pediatrics, s Hopkins Medical Institutions, Baltimore,

land, USA.

The purpose of this review is to analyze the role of reactive oxygen

species (ROS) in the pathogenesis of viral infections, an area of

research that has recently gained momentum given the accumulation of

evidence regarding the role of ROS in the pathogenesis of infection with

the human immunodeficiency virus (HIV). Attention will be focussed on

three classes of viruses: (1) RNA viruses, (2) DNA viruses, and (3)

retroviruses, with particular attention to influenza viruses, hepatitis

B virus, and HIV as representative examples of these three classes,

respectively. For each type of virus, evidence for the following will be

analyzed: (1) the effect of the virus on activation of phagocytic cells

to release ROS and pro-oxidant cytokines such as tumor necrosis factor;

(2) the effect of the virus on the pro-/antioxidant balance in host

cells, including virally induced inhibition of antioxidant enzymes such

as superoxide dismutase and virally induced increases in pro-oxidants

such as nitric oxide; (3) effects of the redox state of the cell on the

genetic composition of the virus as well as ROS-mediated release of host

cell nuclear transcription factor-kappa-B, resulting in increased viral

replication; and (4) efficacy of antioxidants as therapeutic agents in

viral diseases of both animal models and patients.

PMID: 8891667

2: Immunology. 2000 Nov;101(3):300-8.

*Nitric oxide and virus infection.*

Akaike T, Maeda H.

Department of Microbiology, Kumamoto University School of Medicine,

Kumamoto, Japan.

Nitric oxide (NO) has complex and diverse functions in physiological and

pathophysiological phenomena. The mechanisms of many events induced by

NO are now well defined, so that a fundamental understanding of NO

biology is almost established. Accumulated evidence suggests that NO and

oxygen radicals such as superoxide are key molecules in the pathogenesis

of various infectious diseases. NO biosynthesis, particularly through

expression of an inducible NO synthase (iNOS), occurs in a variety of

microbial infections. Although antimicrobial activity of NO is

appreciated for bacteria and protozoa, NO has opposing effects in virus

infections such as influenza virus pneumonia and certain other

neurotropic virus infections. iNOS produces an excessive amount of NO

for long periods, which allows generation of a highly reactive nitrogen

oxide species, peroxynitrite, via a radical coupling reaction of NO with

superoxide. Thus, peroxynitrite causes oxidative tissue injury through

potent oxidation and nitration reactions of various biomolecules. NO

also appears to affect a host's immune response, with immunopathological

consequences. For example, overproduction of NO in virus infections in

mice is reported to suppress type 1 helper T-cell-dependent immune

responses, leading to type 2 helper T-cell-biased immunological host

responses. Thus, NO may be a host response modulator rather than a

simple antiviral agent. The unique biological properties of NO are

further illustrated by our recent data suggesting that viral mutation

and evolution may be accelerated by NO-induced oxidative stress. Here,

we discuss these multiple roles of NO in pathogenesis of virus

infections as related to both non-specific inflammatory responses and

immunological host reactions modulated by NO during infections in vivo.

PMID: 11106932

3: Histol Histopathol. 2005 Jul;20(3):957-67.

*

Role of oxidative damage in the pathogenesis of viral infections of the

nervous system*.

Valyi-Nagy T, Dermody TS.

Department of Pathology, College of Medicine, University of Illinois at

Chicago, Chicago, Illinois, USA.

Oxidative stress, primarily due to increased generation of reactive

oxygen species (ROS) and reactive nitrogen species (RNS), is a feature

of many viral infections. ROS and RNS modulate the permissiveness of

cells to viral replication, regulate host inflammatory and immune

responses, and cause oxidative damage to both host tissue and progeny

virus. The lipid-rich nervous system is particularly susceptible to

lipid peroxidation, an autocatalytic process that damages

lipid-containing structures and yields reactive by-products, which can

covalently modify and damage cellular macromolecules. Oxidative injury

is a component of acute encephalitis caused by herpes simplex virus type

1 and reovirus, neurodegenerative disease caused by human

immunodeficiency virus and murine leukemia virus, and subacute

sclerosing panencephalitis caused by measles virus. The extent to which

oxidative damage plays a beneficial role for the host by limiting viral

replication is largely unknown. An enhanced understanding of the role of

oxidative damage in viral infections of the nervous system may lead to

therapeutic strategies to reduce tissue damage during viral infection

without impeding the host antiviral response.

PMID: 15944946

**.*