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Varicella zoster virus(VZV):
The Varicella-zoster virus (VZV) is one of the eight herpes viruses
known to affect humans (and other vertebrates).
Primary VZV infection results in chickenpox (Varicella), which may
rarely result in complications including VZV encephalitis or
pneumonia.
Even when clinical symptoms of varicella have resolved, VZV remains
dormant in the nervous system of the host in the trigeminal and dorsal
root ganglia.
In about 10-20% of cases, VZV reactivates later in life to produce
herpes zoster (shingles) and its associated sequalae including:
post-herpetic neuralgia, zoster multiplex, myelitis, herpes
ophthalmicus, or zoster sine herpete.
Primary infection (airborne) due to herpes varicella-zoster usually
affects preschool children, causing chickenpox, with rare complications
usually affecting the immunocompromised host. Secondary infection
usually afflicts the elderly when latent viral reactivation occurs,
presumably due to an immune imbalance in the host, and involves the
spread of virus along the skin in the anatomic distribution of nerve
(this disorder is known as shingles).
The virus properties:
- VZV is closely related to the herpes
simplex viruses (HSV), sharing much genome homology. The known envelope
glycoprotein (gB, gC, gE, gH, gI, gK, gL) correspond with those in HSV,
however there is not equivalent of HSV gD.
- VZV virions are spherical and 150-200 nm in diameter.
- Its lipid envelope encloses the nucleo-capsid of 162 capsomeres arranged in a hexagonal form.
- Its DNA is a single linear, double strand molecule, 125,000 nanometers long.
Treatment:
- The virus is very susceptible to disinfectants, notably sodium hypochlorite. Within the body it can be treated by a number of drugs and therapeutic
agents including:
- Acyclovir (Cycloviral)
- Zoster immunoglobulin (ZIG)
- Vidarabine
- Vaccination:
A live attenuated VZV Oka/Merck strain vaccine is available and is
marketed under the trade name Varivax. It was developed by Merck, Sharp
& Dohme in the 1980s from the Oka strain virus isolated and attenuated
by Michiaki Takahashi and colleagues in the 1970s. It was submitted to
the U.S. Food and Drug Administration for approval in 1990 and was
approved in 1995. Since then, it has been added to the recommended
vaccination schedules for children in Australia, the United States, and
many other countries, causing controversy because it is only expected to
be effective for about twenty years, leaving adults vulnerable to the
most dangerous forms of infection by this virus, whereas getting normal
chickenpox as a child typically leaves them immune for life.
Anti-Viral chemotherapy
Antiviral Agents:
Antiviral drugs are available to treat only a few viral
diseases. The reason for this is the fact that viral replication is so
intimately associated with the host cell that any drug that interferes
significantly with viral replication, is likely to be toxic to the host.
Two useful antiviral are:
- The nucleoside analogues
- The interferon
but there are other targets in the different stages of intracellular
viral growth which show potential for antiviral chemotherapy.
Stages in virus replication which are possible targets for
chemotherapeutic agents:
- Attachment to host cell
- Uncoating: (Amantadine)
- Synthesis of viral mRNA: (Interferon)
- Translation of mRNA: (Interferon)
- Replication of viral RNA or DNA: (Nucleoside analogues)
- Maturation of new virus proteins: (Protease inhibitors)
- Budding, release
Nucleotide analogue:
These are synthetic compounds which resemble nucleosides, but have
an incomplete or abnormal deoxy-ribose /or ribose group.
These compounds are phosphorylated to the tri-phosphate form within the
infected cell. In this form, the drug competes with normal nucleotides
for incorporation into viral DNA or RNA. Incorporation into the growing
nucleic acid chain results in irreversible association with the viral
polymerase and chain termination.
Diseases for which effective therapy is available:
- Herpes Simplex virus: Acyclovir (Cycloviral)
- Varicella-Zoster virus : Acyclovir (Cycloviral)
- Cytomegalovirus : Gancyclovir, Foscarnet
- AIDS : Zidovudine, Lamivudine[3TC], Protease inhibitors; incombination
- Respiratory Syncitial virus: Ribavirin
- Influenza : Amantadine
Interferon:
Antiviral agents on which much interest is focused are
the interferon. Interferon are cytokines or lymphokines that regulate
cellular genes concerned with cell division and the functioning of the
immune system. Their formation is strongly induced by virus infection;
they provide the first line of defense against viral infections until
antibodies begin to form. Interferon interfere with the multiplication
of viruses by preventing the translation of early viral messenger RNAs.
As a result, viral capsid proteins cannot be formed and no viral progeny
results.
By far the most effective means of preventing viral diseases is by means
of vaccines. There are two types of antiviral vaccines, inactivated
virus vaccines and attenuated active virus vaccines. Most of the
antiviral vaccines currently in use are of the latter kind. The
principle of antiviral vaccines is that inactivated virulent or active
attenuated virus particles cause the formation of antibodies that
neutralize a virulent virus when it invades the body.
There are three classes: alpha- beta- and gamma
The alpha and beta Interferon:
- They are cytokines which are secreted by virus infected cells.
- They bind to specific receptors on adjacent cells and protect them from infection by viruses.
- They form part of the immediate protective host response to invasion by viruses.
- In addition to these direct antiviral effects, alpha and beta
interferon also enhance the expression of class I and class II MHC
molecules on the surface of infected cells, in this way, enhancing the
presentation of viral antigens to specific immune cells. Their presence
can be demonstrated in body fluids during the acute phase of virus
infection.
Recombinant alpha and beta interferon are now available and have been
used for the treatment of Chronic hepatitis B and C virus infections.
Side effects such as fever, malaise and weight loss have limited the
use.
Gamma Interferon (immune interferon):
- Is a cytokine secreted by TH1 CD4 cells.
- Its function is to enhance specific T cell mediated immune responses.
Mechanism of action of the interferon:
1- Enhancement of the specific immune response:
By increasing the expression of MHC class I molecules on the surface of
infected cells.
The interferon increase the opportunity for specific cytotoxic T cells
to recognize and kill infected cells.
2- Direct antiviral effect:
a) degradation of viral mRNA.
b) inhibition of protein synthesis.
3- Prevents the infection of new cells.
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