VIROLOGY

• Herpesviruses


  • Enveloped double stranded DNA viruses
  • Latent or persistent infection following primary infection
  • Reactivation is common in immunosuppressed
  • Both primary infection and reactivation are likely to be more serious in immunocompromised patients
• Human Herpesviruses


  • HHV 1 (Herpes simplex virus 1 - HSV-1)
  • HHV 2 (Herpes simplex virus 2 - HSV-2)
  • HHV 3 (Varicella-zoster virus - VZV)
  • HHV 4 (Epstein-Barr virus - EBV)
  • HHV 5 (Cytomegalovirus - CMV)
  • HHV 6
  • HHV 7
  • HHV 8 (Kaposi's sarcoma-associated virus)
• Viral Latency


  Latent or persistent infection following primary infection
• Site of Latency


  • Neuronal cells, especially trigeminal ganglia (HSV-1)
  • Neuronal cells, especially sacral dorsal root ganglia (HSV-2)
  • Neuronal cells, especially posterior root ganglia (VZV)
  • B lymphocytes (EBV)
  • Monocytes, macrophages (CMV)
  • T lymphocytes (HHV-6, HHV-7)
  • Not established (HHV-8)
• Common Infections

  • Herpes labialis, herpes whitlow, herpetic keratitis, herpes simplex encephalitis (HSV-1)
  • Herpes genitalis, herpes proctitis, neonatal herpes (HSV-2)
  • Chickenpox, herpes zoster (shingles) (VZV)
  • Infectious mononucleosis, prolonged fever, multiorgan manifestations (EBV)
  • Infectious mononucleosis, prolonged fever (CMV)
  • Febrile illness, roseola (HHV-6, HHV-7)
  • Kaposi's sarcoma (HHV-8)
• Primary infection of HSV

  1. Infects mucoepithelial cells (vesicular lesions)

  2. Short-lived viraemia

  3. Virus disseminated in body and spread to trigeminal ganglia (HSV-1) and sacral ganglia (HSV-2)

  4. Virus establishes latency in neurons
• Reactivation of HSV


  Many triggers can provoke a recurrence (physical or psychological stress, infection, fever, irradiation, sunlight, menstruation)
• HSV-1 causes infection above the belt and HSV-2 below the belt
• 40% of clinical isolates from genital sores are HSV-1, and 5% of strains isolated from the facial area are HSV-2
• Following primary infection, 45% of orally infected individuals and 60% of patients with genital herpes will experience recurrences
• The actual frequency of recurrences varies widely between individuals. The mean number of episodes per year is about 1.6
• Manifestations of Herpes Simplex Virus 1

  • Encephalitis
  • Conjunctivitis
  • Gingivostomatitis
  • Tonsilitis labialis
  • Pharyngitis
  • Esophagitis
  • Herpes gladiatorum
  • Tracheobronchitis
  • Genital herpes
  • Herpes whitlow
• Manifestations of Herpes Simplex Virus 2

  • Meningitis
  • Gingivostomatitis
  • Tonsilitis labialis
  • Pharyngitis
  • Perianal herpes
  • Genital herpes
  • Herpes whitlow
• Herpes labialis (cold sore)


  A recurrence of oral HSV with a prodrome of tingling, warmth or itching at the site, followed by redness, papules and vesicles
• 45% of orally infected individuals will experience reactivation of herpes labialis
• 60% of patients with genital herpes will experience recurrences
• Varicella-Zoster Virus


  • Primary varicella is an endemic disease, highly communicable with an attack rate of 90% in close contacts
  • Most people become infected before adulthood but 10% of young adults remain susceptible
  • Herpes zoster occurs sporadically and evenly throughout the year
• Pathogenesis of Varicella-Zoster Virus

  1. Virus gains entry via respiratory tract and spreads to lymphoid system

  2. After incubation period of 14 days, virus arrives at the skin

  3. Following primary infection, virus remains latent in cerebral or posterior root ganglia

  4. Virus reactivates in ganglion and tracks down sensory nerve to skin, producing varicella rash in dermatome
• Herpes Zoster


  Reactivation of latent virus in a sensory ganglion, tracking down the sensory nerve to the appropriate skin segment, resulting in a characteristic eruption of vesicles in the dermatome often accompanied by intense pain
• Herpes zoster poses a far greater problem in immunocompromised patients in whom the reactivation is more likely
• Treatment of Varicella and Herpes Zoster

  1. Uncomplicated varicella is self-limited and requires no specific treatment

  2. Acyclovir should be given promptly to immunocompromised individuals with varicella and those with serious complications

  3. Acyclovir, valacyclovir, and famciclovir can be used for treatment of herpes zoster
• Cytomegalovirus (CMV)


  • One of the most successful human pathogens
  • Once infected, the person carries the virus for life which may be reactivated
  • Reactivation can lead to vertical transmission
• Modes of CMV transmission

  • Blood transfusions
  • Organ transplants
  • Respiratory droplets
  • Saliva
  • Sexual contact
  • Urine
• Congenital CMV infection may result in cytomegalic inclusion disease
• Severe CMV disease

  • CMV pneumonitis
  • CMV colitis
  • CMV encephalopathy
  • CMV retinitis
• Mononucleosis


  Caused by CMV, symptoms include fever, fatigue, sore throat, swollen lymph glands
• Epstein-Barr Virus (EBV)


  • In developing countries, infection occurs at a much earlier age with 90% of children seropositive by age 2
  • Transmitted by contact with saliva, particularly through kissing
• Burkitt's lymphoma occurs endemically in parts of Africa and Papua New Guinea, usually in children aged 3-14 years, and is restricted to areas with malaria
• Multiple copies of EBV genome and some EBV antigens can be found in Burkitt's lymphoma cells
• Nasopharyngeal carcinoma is a malignant tumour of the nasopharynx very prevalent in South China, with multiple copies of EBV genome found in the tumour cells
• Kaposi's Sarcoma-Associated Virus (HHV-8)


  • HHV-8 DNA is found in almost 100% of cases of Kaposi's sarcoma
  • Most patients with KS have antibodies against HHV-8
  • The seroprevalence of HHV-8 is low in the general population but high in groups susceptible to KS, such as homosexuals