Viruses may be defined as “acellular” organisms whose
genomes1 consist of nucleic acid, and which obligately2
replicate (duplicate themselves) inside host cells using the
host’s metabolic machinery and ribosomes to form a pool
of components which they can assemble into particles
called VIRIONS3. The virons serve to protect the genome
and to facilitate its transfer to other cells.
By older, more zoologically and botanically biased criteria,
then, viruses are not living organisms. However, because
they most definitely replicate, their evolution can (within
limits) be traced and they are independent in terms of not
being limited to a single organism (host), or even
necessarily to a single species, genus or phylum of host, Therefore, in this sense, they must be considered
“living” even though they cannot replicate without infecting a host organism.
A virus is not alive…nor is it dead
A virus is not a bacterium, nor, as we have described, an independently-living organism. A virus cannot
survive in the absence of a living host cell in which it can synthesize copies of itself (replicate). Viruses are
not made of cells, do not eat and do not grow.
Antibiotics, which operate extra-cellularly (outside of a cell) obviously do not harm a virus. It is for this
reason that treatments for the "flu", for example, mainly to help ease the symptoms of the illness rather
than killing the organism which causes the "flu" (An influenza virus is pictured above left.)
A virus has fundamental information (genes made of DNA or RNA) that allows it to make copies of itself.
However, the virus must be inside a living cell of some kind before the information can be used. In fact,
this encoded information won't be made available unless the virus enters a living cell. When a virus enters
into a cell, we call this a “viral infection”. The virus is very, very small relative to the size of a living cell.
Therefore, the information the virus carries is actually not enough to allow it to make copies of itself
(replicate). So, the virus uses the cell's machinery, and some of the invaded cell's enzymes, to create virus
parts which are later assembled into thousands of new, mature, infectious viruses that can leave the host
cell to infect other cells. Poliomyelitis virus, for example, may make over one million copies of its basic
genetic information (RNA) inside a single, infected human intestinal cell!
Moving from the outside to the inside, here
are some of the common parts of a virus:
Capsid (core, genetic material - DNA or
RNA: The capsid is the outer shell of the
virus which encloses the genetic material
within. The capsid is actually made of many,
many identical individual proteins that are
assembled very precisely to form the capsid
structure. Sometimes there will be a protein
core underneath the capsid that also
surrounds the genetic material.
Envelope: Some viruses may have an
additional covering on the outside called a
liquid envelope. An envelope is kind of like
skin around the outside of the virus. The
envelope is actually a lipid bilayer
(membrane) with proteins embedded within
the membrane. If you examine a baseball,
and take it apart, you will see how some viruses are assembled. The cover of the baseball (envelope), the
tightly-woven thread (capsid), and the rubber core (genetic material) can be used to represent the parts of
some viruses.
All viruses only exist to make more viruses.
With the possible exception of bacterial viruses, which kill harmful bacteria, all viruses appear to be
harmful because their replication leads to the death of the host cell that the virus has invaded.
A virus enters the cell by first attaching to a specific structure on the cell's surface using a specific structure
on the virus surface. Depending on the virus, either the entire virus enters the cell, or perhaps only the
genetic material of the virus is injected into the cell. In either case however, the ultimate result of viral
infection is the spread of virus genetic material inside the host cell. Then, the virus material essentially
"takes over" the cell and nothing but viral parts are made, which assemble themselves into many more
complete viruses. These viruses are mature and leave the cell either by a process called "budding", (where
just one or a few viruses at a time leave the cell), or by a process called “lysis”, (where the cellular
membrane ruptures and releases all of the virus particles at once). A complete explanation of the process
is described in detail below.
Types of Virus Life Cycles:
Lytic cycle
1. The virus injects genetic material into the host’s cell.
2. The virus forces host cell’s DNA to make more viral DNA.
3. The host cell makes more copies of the virus protein coat and assembles new viruses.
4. The host cell swells with new viruses particles and bursts open, releasing many new viral particles
that spread to infect other cells.
lysogenic cycle
1. The virus injects DNA into host cell BUT does not start making new viruses right away.
2. The viral DNA is incorporated into the host cell’s DNA (the viral DNA is now called a provirus.)
3. Every time the host cell DNA is copied before mitosis (cell division), the viral DNA is also copied.
4. At some point, the viral DNA becomes active and takes over all the host cells and then instructs
the host cell to make more viruses.
Humans have some protection from viruses
If a particular virus infects one or more cells in tissues in the body, the infection leads to the synthesis and
secretion of substances called “interferons”. Interferons are proteins and may be designated as alpha,
beta, or gamma interferon proteins. These proteins interact with the cells that are adjacent to infected
cells and help these adjacent cells become more resistant to infection by the virus. (An interferon
molecule is pictured below left.)
Sometimes, this resistance isn't quite good
enough to prevent the spread of the virus to
more and more cells, and we begin to feel
sick. Now, however, the body's immune
system takes over and begins to fight the virus
infection by killing the virus as it leaves the
cells (on the outside of the cells), Immune
cells also destroy infected cells. This is
accomplished by our body’s “front line”
warriors called “white blood cells” or “T cells”.
(See picture at right of a white blood cell
surrounded by red blood cells.)
The killing of infected cells prevents the spread of the virus, since as was
stated above, a virus requires a living cell in order for the virus to be able
to replicate. Eventually, a virus will be completely removed, and we are
able get over the illness.
In some cases, however, we do not regain control over virus infections.
HIV is an exception to this situation because HIV infects the cells of the
immune system which are needed to kill infected cells. So, although HIV
does not itself directly cause the condition known as AIDS, the eventual
death of immune cells, because of the virus infection, allows other
infections to harm a person. Herpes simplex is another virus that infects
the immune system. (See Herpes virus pictured at left.)
Virus Replication
Genomes of RNA or DNA viruses exist in a considerable variety of sizes and shapes, from small molecules
of single-stranded RNA or DNA to large double-stranded molecules that may be linear or circular.
Whatever their physical nature, viral RNA or DNA molecules must be replicated efficiently within an
infected cell to provide genomes for assembly into progeny virions. Steps in the Replicative Cycle of
viruses are still composed of six major steps:
1. Attachment or Adsorption
2. Penetration
3. Uncoating
4. Biosynthesis
5. Assembly
6. Release
Maturation
1. ATTACHMENT or ADSORPTION
Virus attachment occurs when a VIRAL ATTACHMENT PROTEIN (VAP) binds to a cellular RECEPTOR. Many
examples of virus receptors are now known. Receptor molecules may be proteins (usually glycoproteins -
specific molecules), or the sugar residues present on glycoproteins or glycolipids (less specific). Some
complex viruses (like the Poxviruses and Herpes viruses) may have more than one receptor or receptorbinding
protein, therefore, there may be alternative routes that the virus takes into cells.
The expression (or absence) of receptors on the surface of cells largely determines the TROPISM of most
viruses. (TROPISM refers to the type of cell in which viruses are able to replicate.) Attachment is, in most
cases, a reversible process. If virus penetration does not occur, the virus can release itself from the cell’s
surface to try and find a new host cell to invade.
2. PENETRATION
Unlike attachment, viral penetration is an energy-dependent process. This means that the cell must be
metabolically active for this to occur. Three mechanisms may be involved:
1. TRANSLOCATION (the complete penetration) of the entire virion through the host cell’s membrane,
2. ENDOCYTOSIS of the virus into intracellular vacuoles; eventually into the cytoplasm. (“Endocytosis”
is a process of cellular ingestion by which the plasma membrane of the host cell folds inward to
allow the virus into the cell.)
3. FUSION of the viral envelope with the cell membrane. This requires the presence of a viral fusion
protein in the virus envelope.
3. UNCOATING
“Uncoating” is a general term that explains the events that occur after viral penetration. First, the capsid is
removed and the virus genome is exposed, usually in the form of a nucleoprotein complex. This might be
relatively simple in structure. Picorna viruses, for example, have a small basic protein of only 23 amino
acids. Retrovirus cores are highly ordered nucleoprotein complexes which contain, in addition to the RNA
genome, other enzymes responsible for converting the viral RNA genome into the DNA PROVIRUS. This
process occurs inside the core particle. They can contain hundreds of amino acids.
For viruses which replicate in the cytoplasm, like the Picorna viruses, the genome is simply released into
the cell. But for viruses which replicate in the nucleus, like the Herpes viruses, the genome, often with
associated nucleoproteins, must be transported through the nuclear membrane. At the nuclear pores, the
capsid is stripped off by the virus, and the virus genome passes directly into the nucleus.
4. BIOSYNTHESIS: GENOME REPLICATION & GENE
EXPRESSION
The replication strategy of the virus depends on the nature of its genome. Viruses can be classified into
seven (arbitrary) groups:
1: Double-stranded DNA (Adeno viruses, Herpes viruses, Pox viruses Adenoviruses are a group
of viruses that typically cause respiratory illnesses such as a common cold, conjunctivitis, (an infection in
the eye), croup, bronchitis, or pneumonia. In children, adenoviruses usually cause infections in the
respiratory and intestinal tract.
2: Single-stranded (+) sense DNA (Parvoviruses) Parvoviruses are some of the smallest viruses
found in nature. (The name comes from the Latin “parvus” meaning “small”). Parvoviruses can cause
diseases in some animals. Because the viruses require actively reproducing cells in order to replicate, the
type of tissue infected varies by the age of the animal. Canine parvovirus is a particularly deadly disease
among young puppies, causing gastrointestinal tract damage and dehydration as well as a cardiac
syndrome in very young pups. It is spread by contact with an infected dog's feces. Symptoms include
lethargy, severe diarrhea, fever, vomiting, loss of appetite, and dehydration. Humans have their own
strain of parvovirus that can spread rapidly from person to person.
3: Double-stranded RNA (Reoviruses, Birnaviruses, Arboviruses) The Reoviridae (Respiratory
Enteritic Orphan virus) are a family of viruses that includes some viruses that affect the gastrointestinal
system (such as Rotavirus), and some that cause respiratory infections. This virus primarily infects infants
(ages 6 to 24 months). Arboviruses (arthropod-borne viruses) are a large group of viruses that are spread
mainly by blood-sucking insects. In the United States, arboviruses are most commonly spread by
mosquitoes. Birds are often the source of infection for mosquitoes, which can then spread the infection to
horses, other animals, including people. Most people infected with arboviruses have few or no
symptoms, but arboviruses can cause serious and potentially fatal inflammation of the brain (encephalitis)
as well as other complications.
4: Single-stranded (+) sense RNA (Picornaviruses, Togaviruses) Picornaviruses are named
because of their size. (“Pico” in Greek means “very small”) These RNA viruses' are among the most
diverse, (with more than 200 serotypes,) and 'oldest' known viruses. (Temple record from Egypt
from1400 B.C. describe this viral infection.). This viral strain was one of the first to be recognised by
Loeffler and Frosch in1898. Poliomyelitis is a viral disease in this family that was first identified by
Landsteiner and Popper in1909 (though the virus was not isolated until the 1930's. The diseases these
viruses cause are varied, ranging from acute "common-cold"-like illnesses, to chronic infections in
livestock. Two main categories are enteroviruses and rhinoviruses.
5: Single-stranded (-) sense RNA (Orthomyxoviruses, Rhabdoviruses) Orthomyxoviruses include
the influenza viruses from the family Orthomyxoviradae. Various animal species can become infected with
their own specific strains of influenza, and, in some cases, the animal strains may produce mild infections
in humans. Some of the human strains cause the more explosive and severe viral infection forms. The
term "flu" is used to refer to a wide variety of infections, ranging from the common cold to various forms
of enteritis. Until recently, Togaviruses were classified in the same family as the Flaviviruses. Modern
molecular techniques allowed virologists to separate the two families based on gene expression.
Togaviruses are divided into two genera: Alphaviruses (18 members) and Rubivirus (1 member, Rubella).
The Alphaviruses are arthropod-borne, and Rubella virus, which causes Rubella or "German Measles" is
transmitted by the respiratory route.
6: Single-stranded (+) sense RNA with DNA intermediate in life-cycle (Retroviruses)
Retroviruses belong to the Retroviridae family of viruses. The genetic material of retroviruses consists of
ribonucleic acid (RNA), instead of deoxyribonucleic acid (DNA). Retroviruses are known to lead to certain
types of cancers in both humans and animals, as well as a range of viral infections. Human
Immunodeficiency Virus (HIV), the virus that causes Acquired Immune Deficiency Syndrome (AIDS), is
one example of a retrovirus.
Retroviruses are unique in that they reproduce by transcribing themselves into DNA. Reverse
transcriptase, an enzyme within a retrovirus, makes it possible for the retrovirus’ RNA to perform as a
template of sorts for the transcription process. Once transcription has taken place, the viral DNA gains
access to the DNA of a host cell, reproducing along with the cell and the cell’s offspring. Within the cell’s
offspring, referred to as daughter cells, the viral DNA creates RNA replicas of itself. Finally, the RNA
replicas leave the daughter cells after coating themselves with a protein.
Retroviruses reverse the normal cell process, which uses RNA to synthesize DNA. By reversing this
process, retroviruses take up permanent residence in the genetic material of the infected cell. In some
cases, retroviruses destroy the cells they change. Such is the case with the retrovirus HIV. Other
retroviruses cause cells to become cancerous. This is what occurs with certain types of leukemia.
Retroviruses are prone to mutation. For this reason, viruses in this family often become resistant to
antiviral drugs within a relatively short period of time. This level of mutability is one of the reasons cited
for the difficulty scientists face in trying to develop a safe and effective HIV vaccine.
7: Double-stranded DNA with RNA intermediate (Hepadnaviruses, Herpex Simplex viruses)
Hepadnaviruses are a family of viruses that cause liver infections in humans and animals. Viral replication
is accomplished by tight regulation of gene expression. The methods used depend on nature of the virus
genome/replication strategy, There are two recognized genera:
Genus Orthohepadnavirus; type species: Hepatitis B virus
Genus Avihepadnavirus; type species: Duck hepatitis B virus
5. ASSEMBLY
Assembly occurs when all the components necessary for the formation of the mature virion are available
at a particular site in the host cell. During this process, the basic structure of the virus is formed.
The site of assembly varies for different viruses. For examplem Picornaviruses, Poxviruses and Reoviruses
assemble In the cytoplasm. Adenoviruses, Papovaviruses and Parvoviruses assemble in the nucleus.
Retroviruses assemble on the inner surface of the host cell’s membrane.
6. RELEASE
For lytic viruses, (most of non-enveloped viruses), release is a simple process. The host cell breaks open
and releases the virus. Enveloped viruses merge with the host cell’s the lipid membrane and the virus

Lyophyllic Third State Mineral ions have a tremendous surface area compared to elemental minerals, due to their minute particle size. The increase in surface area of the minerals increases their zeta potential, which is the kinetic energy or “life force” that sustains us. Third State Minerals are formed by the digestion of the elemental minerals (first quantum state) in the soil by microorganisms that convert any particular mineral into a waste product that contains the same mineral in a second quantum state. When this waste is mixed with ground water, it is assimilated by plant. Whatever amount of the mineral remains after photosynthesis is stored in the plant in its most bio-available form: the third quantum state. This is the only mineral form that is truly completely bioactive and “organic.”INGREDIENTS: Proprietary Plant-Derived Calcium buds out through the host cell’s membrane. Virion envelope proteins are picked up during this process as
the virus releases itself. Budding may or may not kill the host cell, but the cellular activities are completely
controlled by the virus.
MATURATION
Once the virus has escaped from the host cell, it enters a new stage in its life-cycle; the virus becomes
infectious. For some viruses, assembly and maturation are inseparable. For others, maturation may occur
after the virus has left its host cell.
Oxygen Kills
Anaerobic Microorganisms:
Oxygen’s anti-microbial mechanisms are not completely understood. It is known that the cell envelopes
surrounding many pathogen’s, like bacteria, are made up of polysaccharides and proteins. In gramnegative
pathogenic organisms, fatty acid alkyl chains and helical lipoproteins are present. In acid-fast
bacteria, such as Mycobacterium tuberculosis, one third to one half of the capsule is composed of
complex lipids, (esterified mycolic acid, in addition to normal fatty acids), and glycolipids (sulfolipids,
lipopolysaccharides, mycosides, trehalose mycolates).
ABOVE: Aerobic organisms possess enzymes that deactivate oxygen so that
reactive toxic molecules containing oxygen do not damage the cells.
It is this high lipid content of the cell walls of these pathogenic bacteria that may explain their sensitivity,
and eventual destruction, when exposed to oxygen molecules. Oxygen molecules penetrate these
cellular envelopes and affect the cytoplasmic integrity of these pathogenic organisms. In addition, oxygen
disrupts the metabolic activity of these disease-causing cells.
ABOVE: Unlike aerobic organisms, anaerobic organisms do not possess enzymes
that are able to deactivate oxygen. Thus, reactive toxic molecules containing oxygen, damage the cells’
structural integrity, stop the metabolic processes and bring about cellular destruction and death.
As mentioned above, the outer cytoplasmic membranes of unicellular pathogens are composed of lipids,
proteins, and lipoproteins. These membranes act as a diffusion barrier for water, ions and nutrients.
Research indicates that the membranes are actually a lipid matrix containing randomly distributed globular
proteins that penetrate through the lipid bilayer.
Oxygen reacts with the unsaturated fatty acids of the lipid layer in cellular membranes, forming hydroperoxides.
There is a synergistic effect with cellular- formed H2O2. Lipid peroxidation products include
alkoxyl and peroxyl radicals, singlet oxygen, ozonides, carbonides, carbonyls, alkanes and alkenes.
Oxygen disrupts the integrity of the bacterial cell envelope through oxidation of the phospholipids and
lipoproteins. In fungi, oxygen inhibits cell growth at certain stages. With viruses, the oxygen damages the
viral capsid and disrupts the reproductive cycle by disrupting the virus-to-cell contact with peroxidation.
The weak enzyme coatings on cells that make them vulnerable to invasion by viruses make them
susceptible to oxidation and elimination from the body, which then replaces them with healthy cells.
Basically, oxygen disorganizes membrane
permeability so that the organism’s
nucleic acids and cations leak out and the
cell dies.
In addition, oxygen destroys pathogens in
a number of different ways: oxygen shortcircuits
the processes by which pathogens
create energy; oxygen disturbs the
structure of the bacterial cell wall; oxygen
also interferes with the production of
essential proteins.
A Brief History of Research:
Research confirming oxygen’s role in killing viruses dates back more than 70 years. In
1931, physician Dr. J.R. Perdrau wrote in the National Institute for Medical Research: “In
a second and more striking experiment, an activae filtrate of herpes virus lost its
infectivity …by simple exposure to air…these observations suggest that exposure to air
tends to inactivate the virus of herpes…”4
Dr. P. Ebbesen of the Danish Cancer Society, completed a study on oxygen’s
effectiveness in controlling the growth of viruses. His conclusion: “An evidence is
accumulating that the oxygen tension exerts significant effect on the virus replication in
vitro.”5
In a study funded by the National Institutes of Health and conducted at the School of
Medicine at the University of Southern California, the researchers found: “In conclusion,
our results show that ROS (Reactive Oxygen Species) can rapidly inhibit HCV RNA
replication in human hepatoma cells. The increased ROS levels in hepatitis C patients
may therefore play an important role in the suppression of HCV replication.”6
What is ASO® Activated Oxygen?
ASO® is a unique formulation of activated oxygen in a saline base. Unlike its
predecessors, which have used either hydrogen peroxide or chlorine bound oxygen
molecules, ASO® is a natural product containing bio-available oxygen. ASO® is the
world’s premiere stabilized oxygen supplement. It’s been the best for almost a decade! The chemical
components in ASO® are distilled water, sodium chloride (from sea salt), bio-available oxygen and
essential and trace minerals. Other liquid-stabilized oxygen supplements bond their “active” oxygen to
salt molecules forming oxychlorine or oxy-halogen compounds, which drive up the pH of these
supplements to levels that could be dangerous to the skin and delicate membranes in the oral cavity if
taken improperly.
ASO® is:
• an all-natural supplement
• contains one of the highest concentrations of activated oxygen available today.
• Ph balanced (app. 7.4)
• Contains no chlorite molecules
• Non-toxic and safe to use both orally and topically
Importance of pH in selecting an oxygen-enhanced dietary
supplement.
ASO® Activated Oxygen is pH balanced (approximately 7.4). Other stabilized oxygen products are based
on oxychlorine compounds and contain sodium chlorite, which results in high ph values, normally in
excess of 10. To neutralize the high pH of these products, the body must manufacture and release higher
concentrations of hydrochloric acid in the stomach that reacts with the chlorite ion to create a chlorine and
diatomic oxygen molecule. It is only when these molecules are broken up that the oxygen can
theoretically get into the blood stream.
ASO®, however, contains bio-available oxygen and does not depend on the digestive process to be
absorbed. In fact, it can also be safely taken sublingually. If these chlorite-based supplements are not
adequately diluted in water before consuming, the oxychlorine compounds can damage sensitive
membranes before the stomach has a chance to begin the neutralization process. This is especially a
concern for individuals who have problems secreting sufficient amounts of stomach acid (hydrochloric
acid). The stomach may also overproduce stomach acid in an attempt to neutralize these chlorine-based
stabilized oxygen products. This overproduction may irritate the stomach. ASO® contains no chlorite
molecules.
ASO® As a Biocidal Agent:
Extensive independent laboratory tests using ASO® in varying strengths has confirmed its ability to kill
microorganisms. Tests conducted by Nelson Laboratories demonstrated ASO®’s killing affect on
Staphylococcus aureus, Salmonella cholerasuis, Pseudomonas aeruginosa, Escherichia Coli, Candida
albicans, Aspergillus niger and Aspergillus flavus. SGS U.S. Testing Company completed minimum
inhibitory tests using ASO® that demonstrated it controlled Escherichia coli 0157:H7, Pseudomonas
aeruginosa, Salmonella choleraesuis and Staphylococcus aureus.
Research conducted By Dr. Michael Yoshimura, Ph.D. at California Polytechnic State University, School of
Biological Sciences, Phytopathology Department, indicated that ASO® effectively prevented the
germination, or growth of bacteria, and plant pathogens, (especially the pathogen Alterneria blight, on
Zinnea seeds.)
Research done by the University of Minnesota’s Agronomy and Soils Department indicated that when
ASO® was used as a sol drench on celery and parsley seeds, these crops had a higher germination rate. In
addition, when used as a biocidal agent on sugar beet seedlings, the ASO® was more effective in
controlling Aphenomyces, (a soil borne disease that attacks sugar beets,) than a standard treatment called
Tachigaren, The ASO® also helped prevent frost damage on sugar beet seedlings.
Another study conducted at California Polytechnic State University, Food Processing Department, tested
ASO®’s ability, as a soaking agent, to reduce mold and yeast colonies on Cat’s Claw, a botanical used in
the nutritional industry derived from the bark of the Uncaria tomentosa tree grown in Brazil. The tests
indicate clearly that ASO® is very effective when used as a sanitizing disinfectant on the bark reducing the
colony counts by as much as 90% after five minutes of contact.
FOOTNOTES:
1 In biology the genome of an organism is the whole hereditary information of an organism that is
encoded in the DNA (or, for some viruses, RNA). This includes both the genes and the non-coding
sequences. The term was first coined, in 1920, by Hans Winkler, Professor of Botany at the University of
Hamburg.
2 Able to exist or survive only in a particular environment or by assuming a particular role.
3 A complete virus particle, known as a virion, is little more than a gene transporter, consisting in its
simplest form of nucleic acid surrounded by a protective coat of protein called a capsid. A capsid is
composed of proteins encoded by the viral genome and its shape serves as the basis for morphological
distinction. Virally coded protein subunits - sometimes called protomers - will self-assemble to form the
capsid, generally requiring the presence of the virus genome - however, many complex viruses code for
proteins which assist in the construction of their capsid.[5] Proteins associated with nucleic acid are known
as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a
nucleocapsid. [Prescott, L (1993). Microbiology. Wm. C. Brown Publishers. 0-697-01372-3]
4 “Oxygen’s Role in Controlling Viruses: Inactivation and Reactivation of the Virus of Herpes”, J. R.
Perdrau, Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character,
Vol. 109, No. 762 (Nov. 3, 1931), pp. 304-308
5 “Oxygen tension and virus replication.”Ebbesen P, Zachar V., Department of Virus and Cancer, Danish
Cancer Society, Aarhus, Denmark. Acta Virol. 1998 Dec: 42(6):417-21. PMID: 10358750
An evidence is accumulating that the oxygen tension exerts significant effect on the virus replication in
vitro. When the in vitro oxygen tension is maintained at an in vivo physiological level, as a rule higher
yields of human viruses are seen that at conventional culturing with access of an unphysiologically high
oxygen concentration in ambient air. Although not fully understood, possible explanation for this
phenomenon may be provided by a lowered interferon (IFN) output and increased cell replication which is
often optimal at physiological oxygen tension. Furthermore, an indirect evidence suggests that the
expression of some virus receptors is affected by oxygen tension. Also, the antiviral cell-mediated
immunity is likely to be found oxygen tension-dependent as both the NK and cytotoxic T cell activities
towards uninfected target cells are oxygen tension-sensitive. At present, the in vitro work with viruses at
physiological oxygen tensions is hampered by the fact that cells adapt in the course of several weeks to
the new oxygen tension. Whether viruses may adapt to different oxygen tensions is not clear.
Workbenches combining safety in manipulation with hazardous viruses and the convenience of controlled
gas atmosphere during both manipulation and long-term incubation have been developed. It is
suggested that the in vitro virology should ensure that the physiological oxygen tension is better
mimicked in the in vivo processes. Much work is to be done to determine the molecular interactions
between oxygen tension-sensitive elements of the cell and infecting viruses. Of no lesser importance are
the questions regarding the role of oxygen in virus tissue tropism, the cost-benefit of virus production at
different oxygen tension levels, and the potential significance of oxygen tension for delivering gene
effects to the selected target tissues.
6 “Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells”
Jinah Choi, Ki Jeong Lee, Yanyan Zheng, Ardath K. Yamaga, Michael M.C. Lai, Jing-hsiung Ou.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern
California, Los Angeles, CA and the Department of Pediatrics, Keck School of Medicine, University of
Southern California, Los Angeles, CA. Funded by: American Cancer Society; Grant Number: PF-01-037-01-
MBC, National Institutes of Health
Abstract:
Hepatitis C virus (HCV) is a positive-stranded RNA virus that causes severe liver diseases, such as cirrhosis
and hepatocellular carcinoma. HCV uses an RNA-dependent RNA polymerase to replicate its genome and
an internal ribosomal entry site to translate its proteins. HCV infection is characterized by an increase in
the concentrations of reactive oxygen species (ROS), the effect of which on HCV replication has yet to be
determined. In this report, we investigated the effect of ROS on HCV replication, using a bicistronic
subgenomic RNA replicon and a genomic RNA that can replicate in human hepatoma cells. The treatment
with peroxide at concentrations that did not deplete intracellular glutathione or induce cell death resulted
in significant decreases in the HCV RNA level in the cells. This response could be partially reversed by the
antioxidant N-acetylcysteine. Further studies indicated that such a suppressive response to ROS was not
due to the suppression of HCV protein synthesis or the destabilization of HCV RNA. Rather, it occurred
rapidly at the level of RNA replication. ROS appeared to disrupt active HCV replication complexes, as they
reduced the amount of NS3 and NS5A in the subcellular fraction where active HCV RNA replication
complexes were found. In conclusion, our results show that ROS can rapidly inhibit HCV RNA replication
in human hepatoma cells. The increased ROS levels in hepatitis C patients may therefore play an
important role in the suppression of HCV replication. (HEPATOLOGY 2004;39:81-89.)
This information is not intended to treat, cure, prevent or diagnose any disease or medical condition.
Always consult with a medical professional before taking any dietary supplement or using any alternative
modality, especially if pregnant, nursing, taking prescription medications or if you are under a doctor’s
medical care.