Viruses - Introduction

• A large number of viruses that can cause human diseases have been described.
  • Some of these diseases have oro-facial manifestations and will be enountered by dental surgeons during the care of patients.
• Viruses exhibit some fundamental differences from bacteria. These differences have important implications with respect to:
  • Cross infection control.
  • Laboratory investigations.
  • Anti-viral drugs.
  • Vaccination.

   

Viruses are Different from Bacteria

• Viruses are small compared to bacteria and electron microscopy is required to visualise viruses.
  • Most bacteria can be observed using light microscopy.
• Viruses include small amounts of nucleic acid (DNA or RNA) protected within a small number of viral proteins.
  • Bacteria include DNA and RNA, and are able to produce a greater number of different proteins.
  • A small genome size limits how many proteins can be made. The following examples illustrate the huge differences in genome sizes:
    • Hepatitis B Virus - 3,215 base pairs (bp) of DNA.
    • Human Immunodeficiency Virus-1 - 9181 bp of DNA (2.8 x larger than Hepatitis B Virus).
    • Staphylococcus aureus - 2,813,641 bp of DNA (875 x larger than Hepatitis B Virus).
    • Mycobacterium tuberculosis - 4,411,529 bp of DNA (1,372 x larger than Hepatitis B Virus).
    • Fruitfly - 137,000,000 bp of DNA - (42,600 x larger than Hepatitis B Virus).
    • Humans - 3,000,000,000 bp (3 billion bp) of DNA (933,000 x larger than Hepatitis B Virus).
• Viruses are obligate intracellular parasites that require a specific live host for energy production and replication.
  • Most bacteria are able to produce energy independently and are not reliant on host cells for either energy production or replication.
  • Some viruses infect bacteria.
• Viruses dissociate into their constituent components upon entry into a host cell that will be used for replication. The nucleic acid (DNA or RNA) is separated from the viral proteins. The virus then 'hijacks' the normal cellular processes to synthesize large amounts of different viral components (nucleic acids and proteins). These viral components are then assembled into new, infectious viruses.
  • Bacteria maintain their integrity throughout the replication process.
• Viruses rarely produce toxins, but cause tissue damage by the direct effects of virus replication in the cell (causing cell damage and death) and the indirect tissue damage caused by the immune system trying to eliminate intracellular virus.
  • Much of the pathogenicity of bacteria can be attributed to toxins.

1. Cross Infection Control

• Viral infections are often asymptomatic, and it will not be apparent whether:
  • The patient sitting in your dental chair poses risks to your health.
• You pose an infection risk to your staff or patients.
• Even though at a given timepoint a viral infection may be asymptomatic:
  • It may become life-threatening in the future.
  • It may be life-threatening if passed to someone else.
• Because viruses are obligate intracellular parasites they are mostly fragile and cannot survive for long away from their host
  • Particularly if the fluid or cells that they are in dry out.
• The Department of Health has issued advice and guidelines with regard to different aspects of cross infection control.
• The British Dental Association has identified information that is of relevance to the practice of dentistry. This has been published as:
  • 'Infection Control in Dentistry' (BDA Advice Sheet A12).
    • The most recent edition was published in December 1999.
    • This is free of charge to BDA members.
      • Paper copies will be sent out on request.
      • Electronic copies can be downloaded from the web: www.bda-dentistry.org.uk (go to 'BDA advice sheets').
    • This document does not just represent guidelines, but the minimum standards of cross infection control required by law.
    • Be familiar with the contents of this document and adapt your practices accordingly.
• Blood-borne Virus (BBV) infections pose a potentially serious hazard to the dental team.
  • Further information about these important issues are considered in a separate page:
    • Inoculation Injuries.

2. Laboratory Investigation of Viral Infections

• The diagnosis of many viral infections is made on clinical grounds alone. However, laboratory-based investigations are necessary:
  • To establish the cause of serious infections (e.g. HIV or Hepatitis B).
  • When there is doubt over the diagnosis (e.g. to distinguish between the different causes of Glandular Fever-Like Syndromes).
• The use of laboratory investigations in this way reflects limitations of many of the tests.
  • Some of these limitations are discussed below.
• Invstigations can be divided into two broad categories:
  • Investigations that detect the virus or components of the virus.
  • Investigations that detect the host responses to the virus.

A. Detection of the Virus or Viral Components

• Culture of virus from infected secretions or tissues.
  • However, this requires viral transport medium, rapid delivery of the specimen to the laboratory and specialised cell culture techniques. Not all pathogenic viruses can be cultured. Results are not instant, and will not be available to plan early management of the clinical illness.
• Electron microscopy - some viruses have distinctive appearances and results can be obtained rapidly.
  • However, there is only limited availability of the service, it is expensive, requires a high titre of virus to be present and it is not able to specifically identify some viruses.
• Detection of viral antigens with specific antibodies. The sample can be either cytology specimens or less commonly tissue sections.
  • There are cost and technical limitations to these approaches.
• Detection of viral nucleic acid (DNA or RNA) - e.g. Polymerase Chain Reaction (PCR).
  • There are cost and technical limitations to these approaches.

B. Detection of the Host Response to Viral Infection

• Detection of specific anti-virus antibodies for a given infection (e.g. antibodies against HIV antigens) is a powerful way of detecting a specific viral infection, but interpretation must be made with care:
  • The presence of specific antibodies confirms infection with that virus (seroconversion).
    • But, seroconversion takes time (days or weeks), and so results are often not available to help plan initial treatment during the acute illness.
  • After seroconversion some antibodies (usually IgG) persist for life and so it may not be clear if infection occurred either recently or years ago.
  • Detection of specific IgM indicates either a recent primary infection or possibly reactivation of viruses that have a latent state.
  • A fourfold rise in the titres of specific antibodies between the onset of the clinical illness and four weeks later is a useful way of retrospectively confirming a recent infection.
  • In some instances, serology results can be difficult to interpret.
• Detection of specific antibodies induced by viral infection, but not raised against viral antigens, can be useful:
  • Detection of heterophile antibodies (Monospot test) is a useful marker of Infectious Mononucleosis as interpretetation of anti-EBV antibodies can be difficult.
• EBV infection induces an atypical lymphocytosis that can be detected in a Full Blood Count.
• Light microscopy - CMV causes an increase in cell size (cytomegaly) and cells with a distinctive 'owls eye' appearance due to a large basophilic nuclear inclusion body.
  • However, these changes are non-specific and other investigations are necessary to confirm the diagnosis.

3. Anti-Viral Drugs

• Development of anti-viral drugs has been limited compared to the generation of antibiotics to fight bacterial infections.
  • Many antimicrobial drugs only act during microbial replication.
  • Viral replication is dependent upon normal cellular processes (such as protein synthesis) in the host cell, so it is difficult to target the virus without also causing toxicity to the host cell.
• Aciclovir is the only anti-viral drug included in the Dental Practitioners Formulary (DPF).

Aciclovir

• Two aciclovir preparations are included in the DPF (check the current edition for further information):
  • 5% aciclovir cream can be either
    • Prescribed, or
    • Purchased from a pharmacy without a prescription.
  • Aciclovir tablets (200mg) are a prescription only medicine.
• Aciclovir can also be injected intravenously, but this preparation is not included in the DPF.
• Dental practitioners will mainly use aciclovir for the control of HSV infections. Aciclovir can also be useful in VZV infections.
  • The use of aciclovir in these infections has been considered further in the HSV and VZV pages.
  • Whilst aciclovir can control clinical symptoms due to either HSV or VZV infections, it cannot eliminate the latent infection.
• Aciclovir achieves its anti-viral effects in the following way:
  • Some Herpes viruses include a thymidine kinase that converts aciclovir to a monophosphate form.
  • The host cell then phosphorylates the monophosphate to a triphosphate form.
  • The triphosphate form inhibits viral DNA polymerase and prevents synthesis of viral DNA, stopping viral replication.
• HSV can become resistant to aciclovir, especially after use of topical preparations.

4. Vaccination Against Viruses

• Production of effective vaccines against viral infections has been driven by different factors including:
  • The concept that prevention is better than cure.
  • That some viruses cause life-threatening illnesses that cannot be cured (e.g. HIV or hepatitis B).
  • That some viruses cause lifelong infection and may reactivate to produce symptomatic disease long after the primary infection (e.g. the Human Herpes Viruses).
  • The recognition that some viruses can cause cancer (e.g. Human Papillomavirus).
  • That usable anti-viral drugs have been difficult to produce.
• Vaccination programmes against viral diseases have produced some major successes.
  • The eradication of smallpox by vaccination was a major triumph of the 20th century.
  • Many childhood diseases can be effectively prevented by vaccination (e.g. polio, measles, mumps, rubella).
  • Vaccination of health care workers against Hepatitis B has reduced transmission of this potentially lethal virus in the health care setting.
• Some vaccines have become controversial:
  • Uptake of the combined MMR vaccine (against measles, mumps, rubella) has reduced recently due to fears that it induces autism and inflammatory bowel disease.
    • Consequently, there have been associated increases in measles, mumps and rubella.
  • The Oka strain VZV vaccine to prevent chickenpox and shingles has been commercially available for over 20 years, but has not been included in the United Kingdom immunization programme due to concerns over the longterm sequelae.
• To date, it has not been possible to produce effective vaccines against some major viral pathogens including:
  • Human Immunodeficiency Virus (HIV)
  • Herpes Simplex Viruses 1 & 2 (HSV1 & HSV2)
  • Cytomegalovirus (CMV)
  • Epstein Barr Virus (EBV)
  • Human Papillomavirus (HPV)
  • Hepatitis C
  • Viruses that cause the common cold.
• There are many reasons why it is difficult to manufacture an effective anti-viral vaccine, including:
  • Repeated alteration of viral antigens so that they are not recognised by the immune system.
  • Masking of viral antigens with normal host proteins.
  • Viral proteins mimicking normal host proteins.
  • Viral proteins blocking parts of the immune system, such as antigen presentation.
  • Viral latency where there are only a small numbers of viruses present that do not damage the host cell.

Return to Viral Infections Index