Virology (Viruses, diseases and treatment) - 4

Varicella zoster virus(VZV):

  • Virus classification:
    Group: Group I (dsDNA)
    Family: Herpesviridae
    Subfamily: Alphaherpesvirinae
    Genus: Varicellovirus
    Species: Human herpes virus 3 (HHV-3)

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.


  • 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

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.