How NO limits virus replication is at present unclear.

Thread view:

Enable EMail Alerts

Start New Thread

Thread rating:

Perl Molson - 27 Feb 2005 10:32 GMT

http://vir.sgmjournals.org/cgi/reprint/79/4/825

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

(fragments) more on the above posted site.

Inducible nitric-oxide synthase (iNOS) catalyses the synthesis
of high concentrations of nitric oxide (NO) from larginine
and plays a role in microbicidal and tumoricidal
activities, and in immunopathology (Moncada & Higgs, 1993;
Nathan & Xie, 1994). It may also be important in immune
regulation (Albina et al., 1991; Liew, 1995). The role of NO in
virus infection is, however, controversial (Croen, 1993;
Karupiah et al., 1993; Burkrinsky et al., 1995; Mannick et al.,
1994; Rolph et al., 1996; Adler et al., 1997). Most of these
studies used l-arginine analogues which are competitive
inhibitors of NO synthases. The discrepancy between the
results may be attributable to the non-isoform-selective nature
and the variation in the bioavailability of the inhibitors. By
gene targeting, we have constructed a mouse strain lacking
iNOS (Wei et al., 1995). These mice are highly susceptible to
intracellular parasitic infection. We have now tested the ability
of these mice to resist herpes simplex virus (HSV)-1 infection.

Using inhibitors for NO synthase, NO has been shown to
inhibit the in vitro replication of ectromelia virus, HSV-1,
vaccinia virus, vesicular stomatitis virus and human immunodeÆciency
virus (Croen, 1993; Karupiah et al., 1993; Burkrinsky
et al., 1995; Mannick et al., 1994; Bi & Reiss, 1995). These
inhibitors have also been shown to signiÆcantly exacerbate
ectromelia virus infection (Karupiah et al., 1993), HSV-1-
induced pneumonia (Adler et al., 1997) and inØuenza virusinduced
pneumonia (Akaike et al., 1996). However, treatment
of mice with NOS inhibitors failed to inØuence the course of
vaccina virus (Rolph et al., 1996), inØuenza virus (J. P. Tite & F.
Y. Liew, unpublished), or lymphocytic choriomeningitis virus
(R. M. Zinkernagel & F. Y. Liew, unpublished) infections.

Furthermore, NO appears to protect mice from fatal encephalitis
NO limits virus replication is at present unclear. It is likely that
NO acts as a direct eåector molecule rather than indirectly
through the enhancement of host immune responses because
iNOS-deÆcient mice had reduced resistance to HSV-1 infection
in spite of enhanced Th1 response, which is known to be hostprotective
against this virus.NOcould restrict virus replication
by lysing target cells or by direct damage to viral particles as
it is generally accepted that macrophage activation is important
in determining the outcome of HSV infection, and that
resistance correlates with the ability of macrophages to restrict
HSV replication and dissemination (Johnson, 1964). This
mechanism predicts that NO is important in infections with
macrophages as target cells, but is unlikely to have a major role
against virus infections in which CD8+ killer cells are the main
eåector mechanism. iNOS-deÆcient mice contain similar levels
of CD8+ T cells as heterozygous mice following HSV-1 infection. The
ability of iNOS-deÆcient mice to control low
doses of infection indicates that mechanisms in addition to NO
are involved in the resistance against HSV-1 infection.
Furthermore, macrophages are not the only cell type HSV-1
infects.

A major Ænding in this report is the preferential induction
of Th1 cells in mice deÆcient in iNOS. This is likely to result
from inhibition of IL-12 synthesis by NO. It is now generally
agreed that the balance between Th1 (producing IFN-c) and
Th2 (producing IL-4) subsets of CD4+ T cells determines the
outcome of many infectious and autoimmune diseases (Sher &
Coåman, 1992; Liew, 1992; Mason & Fowell, 1992). Our data
suggest that iNOS is important in maintaining a state of
immunological balance, preventing the overexpansion of Th1
cells which have been implicated in a range of immunopathologies.
They also suggest that iNOS inhibitors may be
useful adjuvants for vaccination where an enhanced Th1 cell
response is essential for protective immunity.

Reply to this Message

Perl Molson - 27 Feb 2005 20:59 GMT

Nitric oxide

>From Wikipedia, the free encyclopedia.

Properties

General
Name     Nitrogen monoxide

image:Nitricoxide.png
Chemical formula     NO
Appearance     Colourless gas

Physical
Formula weight     30.0 amu
Melting point     109 K (-164 C)
Boiling point     121 K (-152 C)
Density     1.3 =97103 kg/m3 (liquid)
Solubility     0.0056 g in 100g water

Thermochemistry
fH0gas     90 kJ/mol
fH0liquid     87.7 kJ/mol
S0gas, 1 bar     211 J/molK

Safety
Ingestion     Used for medicinal purposes but has side effects and
dangerous in overdose
Inhalation     Dangerous, may be fatal.
Skin     Irritant.
Eyes     May cause irritation
More info     Hazardous Chemical Database
(http://ull.chemistry.uakron.edu/erd/chemicals/7/6847.html)

SI units were used where possible. Unless otherwise stated, standard
conditions were used.

Disclaimer and references

The chemical compound nitric oxide is a gas with chemical formula NO.
It is an important signaling molecule in the body of mammals including
humans, one of the few gaseous signaling molecules known. It is also a
toxic air pollutant produced by automobile engines and power plants.

Nitric oxide (NO) should not be confused with nitrous oxide (N2O) or
with nitrogen dioxide (NO2).

The nitric oxide molecule is a free radical which makes it very
reactive and unstable. In air, it quickly reacts with oxygen to form
the poisonous nitrogen dioxide.
Contents [showhide]
1 Production and environmental effects
2 Technical applications
3 Biological functions
4 External links
[edit]

Production and environmental effects

At high temperatures molecular nitrogen and oxygen can combine to form
nitric oxide. A major natural source is lightning. Human activity has
drastically increased the production of nitric oxide in combustion
chambers. One purpose of catalytic converters in cars is to partially
reverse this reaction.

Nitric oxide in the air may later convert to nitric acid which has been
implicated in acid rain. Furthermore, both NO and NO2 participate in
the ozone layer depletion.
[edit]

Technical applications

Nitric oxide has few industrial uses. It is an intermediate of the
Ostwald process which converts ammonia into nitric acid.

Nitric oxide can be used for detecting surface radicals on polymers.
Quenching of surface radicals with nitric oxide results in
incorporation of nitrogen, which can be quantified by means of X-ray
photoelectron spectroscopy.
[edit]

Biological functions

See also: Endothelium-derived relaxing factor (EDRF) and signal
transduction

In the body, nitric oxide is synthesized from arginine and oxygen by
the enzyme nitric oxide synthase (NOS).

The endothelium (inner lining) of blood vessels use nitric oxide to
signal the surrounding smooth muscle to relax, thus dilating the artery
and increasing blood flow. This underlies the action of nitroglycerin,
amyl nitrate and other nitrate derivatives in the treatment of heart
disease: the compounds are converted to nitric oxide (by a process that
is not completely understood) which in turn dilates the coronary artery
(blood vessels around the heart), thereby increasing its blood supply.
Nitric oxide also plays a role in erection of the penis, and explains
the mechanism of sildenafil (Viagra). The effects of the recreational
drugs known as poppers are also thought to be due to nitric oxide.

Macrophages, certain cells of the immune system, produce nitric oxide
in order to kill invading bacteria. Under certain conditions, this can
backfire: fulminant infection (sepsis) causes excess production of
nitric oxide by macrophages, leading to vasodilatation (widening of
blood vessels) and probably being one of the main causes of hypotension
(low blood pressure) in sepsis.

Nitric oxide also serves as a neurotransmitter between nerve cells.
Unlike most other neurotransmitters that only transmit information from
a presynaptic to a postsynaptic neuron, the small nitric oxide molecule
can diffuse all over and can thereby act on several nearby neurons,
even on those not connected by a synapse. It is conjectured that this
process may be involved in memory through the maintenance of long-term
potentiation.

The discovery of the biological functions of nitric oxide in the 1980s
came as a complete surprise and caused quite a stir. Nitric oxide was
named "Molecule of the Year" in 1992 by the journal Science, a Nitric
Oxide Society was founded, and a scientific journal devoted entirely to
nitric oxide was created. The Nobel Prize in Physiology or Medicine in
1998 was awarded to Ferid Murad, Robert F. Furchgott, and Louis Ignarro
for the discovery of the signalling properties of nitric oxide. It is
estimated that yearly about 3,000 scientific articles about the
biological roles of nitric oxide are published.
[edit]

http://en.wikipedia.org/wiki/Nitric_oxide

Reply to this Message