Basic Virology for Dentists

• Many viral infections either present initially as an oral lesion, or they can re-activate and cause repeat presentations with oral lesions.
• Herpangina (enteroviruses):

  • Presents as very painful, grey-ish lesions, which then become vesicles, and then become more ulcerated with surrounding erythema
  • Painful for swallowing and eating
  • Lasts a few days

  
• Oral hairy leukoplakia (Epstein Barr Virus):

  • White stranding on the side of the tongue
  • Classically associated with HIV in severely immunosuppressed patients, but can also be seen in other forms of illness that would cause immunosuppression either due to drugs or the underlying condition, e.g. some of the haematological malignancies

  
• A virus is a submicroscopic entity, consistin of a single nucleic acid surrounded by a protein coat, capable of replication only within the cells of plants or animals.
• Viral structure - nucleic acid:

  • RNA or DNA
  • Single or double stranded
  • RNA/DNA can either be a single molecule or segmented
  • Encode 3-100s of genes
  • Make structural proteins (to form part of new viruses)
  • The proteins that coat the RNA and are used as part of the attachment proteins
  • Make non-structural proteins (e.g. enzymes)
  • Act with cellular enzymes to replicate virus
  • May switch off host cell activities (stop cell from doing what it's supposed to be doing)/block immune system
• Viral structure - capsid:

  • The capsid is the protein coat surrounding the viral DNA or RNA
  • Can be a highly structured sphere or icosohedron
  • Can coat the RNA or DNA directly
• Viral structure - envelope:

  • Some viruses are surrounded by a lipid envelope
  • Acquired from the cell
  • Contains viral proteins which are acquired for the virus to attach to and infect a new cell
  • Non-enveloped viruses attach and infect cell directly via the capsid
• Viral life cycle (Part 1):

  • The virus attaches to the cell with the appropriate receptor on the cell surface and is then incorporated inside the host cell
  • This can happen by endocytosis of the virus, or a direct fusion of the cell membrane with the viral envelope, or the capsid can be released into the cytoplasm
  • Once the capsid's been released it either travels into the cytoplasm or through the cytoplasm and into the nucleus, depending on where the virus carries out its main replication
  • The viral nucleic acid (RNA or DNA) is released from the capsid and undergoes a 2 step process...
• Viral life cycle (Part 2):

  • The viral nucleic acid (RNA/DNA) is released from the capsid and undergoes a 2 step process
  • Transcription of the RNA/DNA to create new nucleic acid
  • Translation where enzymes use RNA as a template to create new proteins (capsid or envelope proteins)
  • The RNA's then bound & assembled to the new capsid proteins. That then buds out of the host cell, picking up envelope proteins on the membrane & is then released into the circulation/airways/neighbouring cells as a progeny virus
  • Either infective straight away, or can undergo maturation prior to becoming infective
• Classification:

  • Viruses cannot be classified by disease
  • Different viruses cause the same symptoms
  • Same virus may cause different disease
  • Some viruses don't normally cause disease
  • Viruses are classified by their nucleic acid and replication strategy
• Double-stranded DNA virus:

  • Herpes viruses (cold sores, chickenpox)
  • Hepatitis B virus (sometimes classified separately though because of its complicated replication process)
  • Adenovirus (URTI, conjunctivitis, diarrhoea)
• Single-stranded RNA virus:

  • Influenza viruses
  • Measles
  • Mumps
  • Rhinovirus (common cold)
  • Hepatitis C virus
• Retroviruses are single-stranded RNA viruses, but because they replicate in a very special way, they have their own classification.
• Retrovirus replication:

  • There's an attachment and fusion of the virus and the host cell and then the injection of the RNA into the cytoplasm. This then goes through a reverse transcription process, which then creates a double-stranded DNA, which is then integrated directly into the host's genome. It's then used as a template to create future proteins and RNA, which are then assembled to create new viruses, which bud off and go on to infect other cells.
  • Basically impossible to treat because they integrate themselves into host cells.

  
• Single-stranded DNA:

  • Parvovirus (childhood rash illness)
• Double-stranded RNA:

  • Rotavirus (childhood diarrhoea)
• Acute pathogenesis:

  • E.g. Measles, mumps, common cold
  • The virus comes along, infects a person, there's rapid replication, it causes a clinical illness which then settles as the host immune system takes control of the virus and clears it from the system
  • Probably the majority of the virus infections we think about
• Persistent pathogenesis:

  • E.g. adenovirus
  • Viruses that cause an acute illness, but then the virus can continue to replicate at low numbers within certain tissues in the body without causing ongoing disease
• Latent pathogenesis:

  • E.g. Herpesvirus family
  • Get an acute infection which can be asymptomatic or clinical presenting, the virus then becomes dormant within certain cells and can sit there for a number of years and periodically reactivate under certain circumstances (asymptomatic or a symptomatic infection)
• Reactivation pathogenesis:

  • E.g. Cold sores, shingles, often asymptomatic
• Tissue damage by virus pathogenesis:

  • E.g. Oral herpes simplex
  • As the virus replicates, it causes the cell to burst open and die (lysis), which causes direct tissue damage (the clinical presentation)
• Secondary damage due to immune reaction to virus pathogenesis:

  • E.g. Acute hepatitis B virus infection
  • The virus can happily replicate within liver cells without causing any significant problems - only problems occur when the immune system notices the virus and goes on to try to clear it - does this by destroying the cells that are infected, leading to acute liver injury
• Infections can be more severe in some groups:

  • The immunocompromised
  • Viral infections usually more severe in the immunosuppressed. Can be life-threatening.
  • Some viruses cause symptoms only in the immunosuppressed
  • Extremes of age
  • Pregnancy
  • Infections may be more severe (e.g. Chickenpox)
  • Infections may affect the foetus (e.g. Rubella, cytomegalovirus)
• Transmission:

  • Respiratory route
  • E.g. influenza, measles, chickenpox
  • Blood exposure
  • E.g. Hepatitis B virus, hepatitis C virus, HIV
  • Needlestick, intravenous drug use, sexual intercourse, splashes (into mucosa, broken skin)
  • Contact - including via fomites
  • E.g. shingles, saliva (EBV, HSV, CMV)
  • Faecal-oral
  • E.g. Enteroviruses, diarrhoea viruses