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Medical Microbiology
Chapter 54
Human Herpesviruses
Human Herpesviruses
Human Herpesviruses – Table 54-1
 Structure:

 Large,
enveloped virus – Figure 54-1
 Double-stranded DNA genome (linear)
Human Herpesviruses

Replication
 Attachment
is very tissue-specific
 Entry by membrane fusion
 Capsid then delivers DNA to the nucleus
 Replication,
 New
transcription, translation
capsids are assembled in the nucleus
(around the replicated DNA)
 They exit the cell by exocytosis or cell lysis
Human Herpesviruses

Herpes Simplex Virus (HSV) was linked to
cold sores in 1919!
 Genome
codes for ~80 proteins
~90% of 2-year-olds in developing
countries have Ab to HSV-1
 ~22% of adults in the US are infected with
HSV-2 (45 million)

 There
are about 1 million new cases per year
Human Herpesviruses

Herpes Simplex Virus (HSV) infection sites:
 Figure

HSV-1 usually causes infections above the
waist
 HSV-2

54-3
usually causes infections below the waist
Symptoms are generated from cell lysis and
cytotoxic T-cell activity
 Antibody
effectiveness is limited
Human Herpesviruses

Infection progression:
 Enters
tissue through breaks in mucous
membranes or skin
 Infects cells at the base of the break
 Replicates and spreads to surrounding tissue
 Sometimes
syncytia are formed to facilitate spread
 Neurons
are infected and the virus travels to
ganglia (trigeminal-oral; sacral;genital)
 The
virus goes into a latent state
Human Herpesviruses
 Reactivation
is triggered by stress, trauma,
fever, menstruation, UV exposure, or a
suppressed immune system
 This
leads to viral replication and movement back
down the nerve to infect the same area
 Subsequent infections are usually more mild
(memory)
Human Herpesviruses

Evasion of the immune system:
 Blocks
effects of interferon
 Blocks the cell machinery that is responsible for
Ag-presentation on the MHC I protein
 Spreads through syncytia to evade Ab
Human Herpesviruses

Transmission (enveloped virus)
 Body
fluids or close contact
 HSV-1 Kissing, sharing glasses, straws,
toothbrushes, etc.
 HSV-2 – Sexual contact or infection at or before
birth
 This
usually leads to very severe neurological
infections and damage in the neonate
Human Herpesviruses
Disease progression – Figure 54-4
 Cold Sores – Figures 54-5 and 54-6
 Genital Herpes – lesions on or around the
genitalia

 Recurrence
is usually preceded by a tingling,
burning sensation
 Then lesions erupt
 This can recur every 2-3 weeks or up to 6
months
Human Herpesviruses

Herpes encephalitis and meningitis
 Causes

significant morbidity and mortality
HSV neonatal infection – often causes
mental retardation and death
 No
functional Cell-Mediated Immunity
Human Herpesviruses
Treatment (acyclovir and others) can lessen
severity and length of disease, but there is
no cure
 No vaccine is available, but they are in
development

Human Herpesviruses

Varicella-Zoster Virus
 Shares
many characteristics with HSV-1
 Latency, lesions, and Cell-mediated immunity
required for clearing
Human Herpesviruses

Disease progression:
 Acquired
by inhalation (droplet transmission)
 Primary infection in mucosa of respiratory tract
 Viremia allows spread to liver, spleen, and other
tissues
 Viral
replication continues
 Secondary
viremia allows spread to the skin
with the formation of “chicken pox”
 This
arise
viremia facilitates spread BEFORE symptoms
 Figures
54-9 and 54-10
Human Herpesviruses
 The
viruses go into latency in the dorsal root
ganglia (or cranial nerve ganglia)
 The virus can be reactivated in older individuals
or patients with impaired cell-mediate immunity
 This causes shingles or “herpes zoster” (zoster
means belt or girdle)
 The
virus only infects the specific dermatome
innervated by the nerve
 Figure 54-11
 Box
54-6
Human Herpesviruses

Epidemiology
 VZV
is extremely communicable (90% rate of
household infection)
 More
than 90% of adults have Ab
 10-20%

Disease is much worse in adults and teens
because immunopathology is worse
 Can

of infected adults will experience zoster
lead to pneumonia and death
Box 54-7
Human Herpesviruses

Treatment – live, attenuated vaccine
Human Herpesviruses

Epstein-Barr Virus (EBV) primarily infects Bcells
 Causes
infectious mononucleosis (“mono”),
Hodgkin’s disease, and a type of cancer called
Burkitt’s lymphoma

EBV infection:
 Replication
in B-cells
 Latency in B-cells
 Immortalize B-cells
Human Herpesviruses

Immuno-competent individuals have mono
 Lack
of effective immune control of EBV leads
to the proliferative diseases

Mono results from a “civil war” between
infected B-cells and T-cells.
 Huge
numbers of lymphocytes in the blood
account for the name (mononucleosis)
 Virus persists in a few B-cells for life!
Human Herpesviruses

EBV is transmitted in saliva
 90%
of EBV-infected persons shed the virus
intermittently for life (even though they are
asymptomatic)!
 70% of US population infected by age 30

Boxes 54-8 and 54-9
Human Herpesviruses

Symptoms of mono:
 Swollen
lymph nodes
 Splenomegaly (enlarged spleen)
 Exudative pharyngitis (sore throat)
 Fever, malaise, FATIGUE

No Treatment