Medical Microbiology & Immunology
Lecture 30 Virology Herpes Viruses I & II
1) To know the herpes viruses that cause human disease.
Herpes simplex virus type 1
Herpes simplex virus type 2
Varicella zoster
Cytomegalovirus
Epstein-Barr virus
Human herpes virus type 6
Human herpes virus type 7
Human herpes virus type 8
2) To describe the morphology, structure and replication of herpes virus.
Morphology - herpes viruses are similar with an overall size of 180 to 200 nm, a
double-stranded DNA core of about 75 nm surrounded by icosahedral capsid, and a
lipoprotein envelope derived from nuclear membrane.
Structure - the simplex viruses (HSV-1 and HSV-2) have 50% sequence homology
and share antigens in almost all their surface glycoproteins and other structural
polypeptides, numerous strains of both exist. Genomic organization consists of alpha
genes (immediate early genes) which encode regulatory proteins, beta genes (early
genes) which encode replication proteins (e.g. DNA polymerase), and gamma chains
(late genes) which encode structural proteins (glycoproteins). Cytomegalovirus is
similar to HSV but contains highly regulated cis-acting elements and regulatory
proteins, with slow replication and slow disease affects, including formation of
inclusion bodies and induction of giant cells.
Replication - DNA is released into the cytoplasm and migrates to the nucleus,
transcription takes place in the nucleus using host RNA polymerase, mRNA is
translated in the cytoplasm to form proteins which are transported back to the
nucleus, viral DNA polymerase completes replication of the viral genome, the virus is
assembled in the nucleus, and buds through the nuclear membrane to obtain an
envelope.
3) To explain clinical disease associated with each herpesvirus.
Herpes simplex virus type 1 - primarily asymptomatic with the cute and latent phases.
Symptoms include: Gingivostomatitis (fever blisters in children), labialis (cold sores),
keratoconjunctivitis, encephalitis, eczema herpaticun, injured skin, and herpetic
whitlow.
Herpes simplex virus type 2 - Vulvovaginitis (genital herpes), progenitals (ulcers on
penis/skin), aseptic meningitis, and neonatal herpes contracted during delivery
(mortality 60%).
Varicella zoster - chickenpox occurrence is generally around 2-8 years of age, occurs
by inhalation, replicates and respiratory tract (incubation 14-18 days), itchy vesicles
containing clear fluid appear on the head, neck, and trunk, associated symptoms
include mild fever, malaise, and headache, recovery in two weeks.
Cytomegalovirus - asymptomatic infection often occurs in childhood and early
adulthood. Infants with congenital infection may appear normal at birth, but may
develop hearing loss or some mental retardation. Infants with symptomatic illness at
birth demonstrate hepatosplenomegaly, jaundice, anemia, low weight, microcephaly,
rash, and thrombocytopenia.
Epstein-Barr virus - usually asymptomatic, however symptoms may include: low
fever, headache, sore throat, fatigue, night shills, and large lymph nodes and spleen,
elevated lymphocytes and monocytes, and atypical lymphocytes. Complications
include: laryngeal obstruction, meningitis, encephalitis, hemolytic anemia,
thrombocytopenia or splenic rupture may occur in 1-5 % of the patients.
Human herpes virus type 6 - the most communicable of all herpes viruses causing
roseola infantum (rash like disease).
Human herpes virus type 7 - not known, however, infects most children by age 2 and
97% of adults are seropositive.
Human herpes virus type 8 - Kaposi's sarcoma associated herpesvirus.
4) To compare lytic and latent infection.
Lytic infection: Actively shedding the virus occurs in the acute stage and in recurrent
infection. This results in the formation of painful blisters that may erupt.
Latent infection: All herpes viruses establish latent infections, although, the site of
latency and features of reactivation are different for each virus. During latent
infection, certain viral proteins are produced, but no complete viral particles. The
genome is present as a circular extra chromosomal element in the nucleus of the
infected cell.
5) To explain latency and reactivation in herpesvirus infection. Reactivation occurs
at the same site as primary infection and is triggered by trauma, fever, sunlight,
excitement, and emotional stress.
6) To discuss the diagnosis, treatment, and prevention of herpesvirus infection.
Diagnosis - some viruses can be isolated in cell culture and biopsy material can be
stained using immunofluorescence. DNA detection is usually accomplished by PCR.
Detection of antibodies can be accomplished through serology testing.
Treatment - antiviral therapy can be helpful. Some antivirals include: acyclovir (most
common), foscarnet, and gancyclovir. Other treatments include supportive therapy,
hyperimmune globulin, and interferon-alpha.
Prevention - most have no vaccine available, so the only prevention method is to
avoid contact with an infected person. Varicella zoster does have a vaccine and
immune globulin can be given for patients at risk.
Virus Infection
Herpes simplex virus
Type 1
Type 2
Varicella-zoster
Cytomegalovirus
Epstein-Barr virus
Human herpes virus
Type 6
Human herpesvirus
Type 7
Human herpesvirus
Type 8
Clinical syndrome
Gingivostomatitis in children and
young adults; recurrent oral labial
infection (cold sores); infection of the
cornea (keratitis); herpes encephalitis
Genital herpes; neonatal herpes
Latent site
Trigeminal nerve root
ganglion and autonomic
ganglia of superior cervical
and vagus nerves
Sacral nerve root herpes
ganglia
Thoracic cervical or lumbar
nerve root
Leukocytes (neutrophils and
lymphocytes)
Diagnostic test
Culture, lesion IFA, lesion
PCR
B lymphocytes
B and T lymphocytes
Serology
Serology
Not known
T lymphocytes
Serology
Kaposi's sarcoma (KS)
Endothelial cells
PCR
Chickenpox (primary infection);
shingles (zoster) ganglia
Asymptomatic infection; heterophilenegative mononucleosis; fever hepatitis
syndrome in neonates and transplant
patients; interstitial pneumonia in
immunocompromised patients
Heterophile positive mononucleosis
Roseola (Exanthem subtium)
Culture, lesion IFA, lesion
PCR
Culture, lesion IFA, lesion
PCR
Culture, blood lung lavage
IFA, lung