Herpesviruses Download

Transcript
Medical biology, microbiology,
virology, immunology department
HERPESVIRUSES.
By as. E.V. Pokryshko
Properties of the Viruses:
All herpesviruses have a
core of double-stranded
DNA surrounded by a
protein coat that exhibits
icosahedral symmetry. The
nucleocapsid is surrounded
by an envelope.
Common and important herpesviruses of
humans include herpes simplex virus types
1 and 2, varicella-zoster virus, EpsteinBarr (EB) virus, and cytomegalovirus.
HERPES SIMPLEX:
Human Herpesvirus 1 (Herpes Labialis) &
Human Herpesvirus 2 (Herpes Genitalis).
Infection with herpes simplex virus may take
several clinical forms. The infection is most
often
inapparent.
The
usual
clinical
manifestation is a vesicular eruption of the skin
or mucous membranes. Infection is sometimes
seen as severe keratitis, meningoencephalitis,
and a disseminated illness of the newborn.
Cytopathic effect (infected cells develop
intranuclear acidophilic inclusion and then
undergo necrosis )
Herpes labialis
(cold sores, herpes febrilis).
This is the most common recurrent
disease produced by type 1. Clusters of
localized vesicles occur, usually at the
mucocutaneous junction of the lips. The
vesicle ruptures, leaving a painful ulcer
that heals without scarring. The lesions
may recur, repeatedly and at various
intervals of time, in the same location.
The permanent site of latent herpes
simplex virus is the trigeminal ganglion.
Herpes labialis
Keratoconjunctivitis.
The initial infection with herpesvirus
may be in the eye, producing severe
keratoconjunctivitis. Recurrent lesions
of the eye appear as dendritic keratitis
or corneal ulcers or as vesicles on the
eyelids. With recurrent keratitis, there
may be progressive involvement of the
corneal
stroma,
with
permanent
opacification and blindness.
Genital herpes (herpes progenitalis).
Genital herpes is characterized by
vesiculoulcerative lesions of the penis of
the male or the cervix, vulva, vagina, and
perineum of the female. The lesions are
more severe during primary infection and
may be associated with fever, malaise,
and inguinal lymphadenopathy.
Type 2 virus remains latent in lumbar and
sacral ganglia.
Neonatal herpes.
Herpesvirus type 2 may be transmitted
to the newborn during birth by contact
with herpetic lesions in the birth canal.
The spectrum of illness produced in the
newborn appears to vary from subclinical
or local to severe generalized disease
with a fatal outcome. Severely affected
infants who survive may have permanent
brain damage.
Laboratory Diagnosis
The virus may be isolated from herpetic lesions
(skin, cornea, or brain).
The appearance of typical cytopathic effects in
cell culture suggests the presence of herpesvirus
in 18-36 hours. Scrapings or swabs from the base
of early herpetic lesions contain multinucleated
giant cells.
Serology: The agent is then identified by
neutralization test or immunofluorescence
staining with specific antiserum. Antibodies
appear in 4-7 days; can be measured by NT, IHT,
CFT, RIA and reach a peak in 2-4 weeks.
HV, immune fluorescence test
VARICELLA-ZOSTER VIRUS
(Human Herpesvirus 3)
(Chickenpox, Herpes Zoster, Shingles, Zona)
Varicella (chickenpox) is a mild, highly infectious
disease, chiefly of children, characterized clinically
by a vesicular eruption of the skin and mucous
membranes. The causative agent is indistinguishable
from the virus of zoster.
Zoster (shingles) is a sporadic, incapacitating
disease of adults (rare in children) that is
characterized by an inflammatory reaction of the
posterior nerve roots and ganglia, accompanied by
crops of vesicles (like those of varicella) over the
skin supplied by the affected sensory nerves.
VARICELLA-ZOSTER VIRUS
(Human Herpesvirus 3)
(Chickenpox, Herpes Zoster, Shingles, Zona)
Both diseases are caused
by the same virus. Varicella
is the acute disease that
follows primary contact with
the virus, whereas zoster is
the response of the partially
immune
host
to
a
reactivation of varicella
virus present in latent form
in sensory ganglia.
Pathogenesis & Pathology.
Varicella: The route of infection is
probably the mucosa of the upper
respiratory tract. The virus probably
circulates in the blood and localizes in the
skin. Swelling of epithelial cells, ballooning
degeneration, and the accumulation of
tissue fluids result in vesicle formation. In
nuclei of infected cells, particularly in the
early stages, eosinophilic inclusion bodies
are found.
Varicella virus, pathogenesis
Varicella
Chickenpox
Pathogenesis & Pathology.
Zoster: In addition to skin lesions —
histopathologically identical with those of
varicella — there is an inflammatory reaction
of the dorsal nerve roots and sensory ganglia.
Often only a single ganglion may be involved.
As a rule, the distribution of lesions in the
skin corresponds closely to the areas of
innervation from an individual dorsal root
ganglion. There is cellular infiltration, necrosis
of nerve cells, and inflammation of the
ganglion sheath.
Zoster
Shingles
CYTOMECALOVIRUS
(Human Herpesvirus 5)
Cytomegalic inclusion disease is a generalized infection
of infants caused by intrauterine or early postnatal
infection with the cytomegaloviruses. The disease causes
severe congenital anomalies. Cytomegalovirus can be
found in the cervix of up to 10% of healthy women.
Cytomegalic inclusion disease is characterized by large
intranuclear inclusions that occur in the salivary glands,
lungs, liver, pancreas, kidneys, endocrine glands, and
occasionally, the brain. Most fatalities occur in children
under 2 years of age. Inapparent infection is common
during
childhood
and
adolescence.
Severe
cytomegalovirus infections are frequently found in adults
receiving immunosuppressive therapy.
Cytomegalovirus Inclusion Diseases.
Electron micrograph of a single animal
cell infected with the cytomegalovirus.
The intranuclear inclusion body has
a typical” owl-eyed” apearence.
Pathogenesis.
Cytomegalovirus
can
cause
persistent
infection in various tissues, including those of
the
salivary
glands,
breasts,
kidneys,
endocervix, seminal vesicles and peripheral
blood leukocytes. This persistent infection leads
to chronic viral excretion by the involved organ.
Transmission of virus is through contact with
infected secretions. The average incubation
period is four to six weeks.
It should also be noted that the kidneys of
organ donors can be a source of cytomegalovirus
for the recipient, and that peripheral blood
leukocytes have been implicated in the
transmission of cytomegalovirus via blood
transfusion.
Clinical Manifestations.
Cytomegalovirus infection can result in
one of three distinct clinical syndromes.
Congenital cytomegalovirus infection:
hepatospleno-megaly, retinitis, a
petechial/purpuric skin rash, and
involvement of the central nervous
system (ventriculo-megaly, intracranial
calcifications, etc).
Clinical Manifestations.
Mononucleosis syndrome (fever, malaise,
atypical lymphocytosis, pharyngitis and,
rarely, cervical adenopathy or hepatitis)
Third clinical entity is cytomegalovirus
infection
in
severely
immunocompromised individuals. In these
patients, infection can involve the lungs,
gastrointestinal tract, liver, retina, and
central nervous system
EB HERPESVIRUS
(Human Herpesvirus 4).
EB (Epstein-Barr) virus is
the causative agent of
infectious mononucleosis and
has been associated with
Burkitt's
lymphoma
and
nasopharyngeal carcinoma.
Epidemiology. Epstein-Barr virus is transmitted
by intimate contact.
Pathogenesis. Epstein-Barr virus is tropic for Blymphocytes.
Infectious
mononucleosis
Nasopharyngeal
carcinoma
Burkitt's lymphoma
Oncogenic Properties:
Herpesviruses have been linked with
malignant diseases in humans : herpes
simplex virus type 2 with cervical and
vulvar carcinoma; EB virus with Burkilt 's
lymphoma of African children and with
nasopharyngeal carcinoma.
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