Microbiology, virology, immunology
department
ARBOVIRUSES.
DNA-VIRUSES:
HERPESVIRUSES.
ADENOVIRUSES
By as. Kuchmak O.B.
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, Epstein-Barr
(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.

acute respiratory disease,
pharyngoconjunctival fever,
nonstreptococcal exudative pharyngitis,
and primary atypical pneumonia
Laboratory Diagnosis.
The viruses have been recovered from
throat swabs, conjunctival swabs, rectal
swabs, stools of patients with acute
pharyngitis and conjunctivitis, and urine
of patients with acute hemorrhagic
cystitis. Virus isolations from the eye are
obtained mainly from patients with
conjunctivitis.
Laboratory Diagnosis.
The viruses are isolated by inoculation of
tissue cultures of human cells in which
characteristic
cytopathic
changes
are
produced.
A new serotype that has not been isolated in
cell cultures can be detected by direct
examination of fecal extracts by electron
microscopy or by enzyme-linked immunosorbent
assay.
Laboratory Diagnosis.
Serology. In most cases, the neutralizing
antibody titer of infected persons shows a 4fold or greater rise against the type
recovered from the patient in NT.
The CF test, using the common antigen, is an
easily applied method for detecting infection
by any member of the group.
A sensitive radioimmunoassay can measure
serum antibody to type 5 fiber antigen.
The arthropod-borne viruses, or arboviruses,
are a group of infectious agents that are transmitted
by blood-sucking arthropods from one vertebrate host
to another.
They can multiply in the tissues of the arthropod
without evidence of disease or damage. The vector
acquires a lifelong infection through the ingestion of
blood from a viremic vertebrate.
All arboviruses have an RNA genome, and most have
a lipid-containing envelope and consequently are
inactivated by ether or sodium deoxycholate.
Current taxonomic status of some arboviruses
Togaviridae
Flaviviridae
Bunyaviridae
Reoviridae
Rhabdoviridae
Arenaviridae
Nodaviridae
Genus Alphavirus
Genus Flavivirus
Genus Bunyavirus
Genus Orbivirus
Genus Vesiculovirus
Genus Arenavirus
Structures of Alphaviruses
Principal medically important alphaviruses
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Distributio
n
Eastern
equine
encephalitis
Encephalitis
(EEE)
Mosquito
Birds
Americas
Western
equine
encephalitis
Encephalitis
(WEE)
Mosquito
Birds
North
America
Venezuelan
equine
encephalitis
Febrile
illness,
encephalitis
(VEE)
Mosquito
Rodents,
horses
Americas
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Distributio
n
Chikungun
y (CHIK)
Febrile
illness, rash,
arthralgia
Mosquito
Primates,
humans
Africa,
India,
Southeast
Asia
O’nyongnyong
(ONN)
Febrile
illness, rash,
arthralgia
Mosquito
Primates
Africa
Sindbisc
(SIN)
Febrile
illness, rash,
arthralgia
Mosquito
Birds
Nothern
Europe,
Africa, Asia,
Australia
Semliki
Forest
Febrile
illness, rare
encephalitis
Mosquito
Birds
Africa
FIGURE Alphavirus transmission. Virus abbreviations:
Chik, chickungunya; RR, Ross River; May, Mayaro; ONN,
O'nyong-nyong; SIN, Sindbis; EEE, eastern equine
encephalitis; VEE, Venezuelan equine encephalitis.
Pathogenesis of alphaviruses
Rubellaviruses
The rubella virus is a member of the genus
Rubivirus in the family Togaviridae.
Rubella
(German measles) is a common mild disease
characterized by a rash. It affects children and
adolescents worldwide and can also affect young
adults.
When rubella virus infects susceptible women
early in pregnancy, it may be transmitted to the
fetus and may cause birth defects. Therefore,
accurate diagnosis is critical in pregnancy.
FIGURE. Clinical findings, virus shedding, and serologic response
in postnatally acquired rubella.
Abnormalities Associated with Congenital
Rubella Syndrome
Type of defects
Examples
Ocular defects
Cataracts
Microphthalmia
Glaucoma
Retinitis
Heart defects
Patent ductus arteriosus
Atrial septal defect
Ventricular septal defect
Peripheral pulmonic artery stenosis
Hearing impairment
Sensorineural deafness
Abnormalities Associated with Congenital
Rubella Syndrome
Type of defects
Examples
Central nervous
system
Mental retardation
Meningoencephalitis
Progressive rubella panencephalitis (rare)
Microcephaly
Other
Growth retardation
Radiolucent borne disease
Hepatosplenomegaly
Hemathologic abnormalities:
Thrombocytopenia, purpura
Pneumonitis
Endocrine dysfunction:
Insulin dependent diabetes mellitus,
thyroididtis
Cataract
Glaucoma
Structure of Flaviviruses
Principal medically important flaviviruses
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Dengue
(DEN)
Febrile
illness, rash,
hemorrhagic
fever, shock
syndrome
Mosquito
Humans
Yellow fever
(YF)
Hemorrhagic
fever,
hepatitis
Mosquito
Primates,
humans
St. Louis
encephalitis
(SLE)
Encephalitis
Mosquito
Birds
Distributio
n
Tropics,
worldwide
Africa,
South
America
Americas
Principal medically important flaviviruses
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Distributio
n
Japanese
encephalitis
(JE)
Encephalitis
Mosquito
Pigs, birds
India,
China,
Japan,
South-East
Asia
Febrile
illness
Mosquito
Birds
Africa,
Middle East,
Europe
Encephalitis
Tick
Rodent
West Nile
Tick-borne
encephalitis
(TBE)
Europa,
Asia
Principal medically important flaviviruses
Virus
Antigenic
Clinical
Syndrome
Vector
Host
Distributio
n
Omsk
hemorrhagic
fever
Hemorrhagi
c fever
Tick
Muskrats
Siberia
Kyasanur
Forest disease
(KFD)
Hemorrhagi
c fever
Tick
Rodents
India
primates
Tick-born encephalitis virus
Human infection with both mosquito-borne and tick-borne
flaviviruses is initiated by deposition of virus through the skin via
the saliva of an infected arthropod (Fig).
Figure. Pathogenesis of flaviviruses.
Yellow fever
Dengue fever
Bunyaviridae is a family of arthropod-borne or
rodent-borne, spherical, enveloped RNA viruses.
Bunyaviruses are responsible for a number of febrile
diseases in humans and other vertebrates. They have
either a rodent host or an arthropod vector and a
vertebrate host.
Human diseases Caused by Viruses
of the Family Bunyaviridae
Genus and
Group
Virus
Diseas
e
Vector
Distributi
on
Bunyavirus
Bunyamwe
ra
Bunyamwera
Fever
Mosquito
Africa
Bwamba
Bwamba
Fever ,
Rash
Mosquito
Africa
California
California
encephalitis
Encepha
-litis
Mosquito
North
America
Simbu
Shuni
Fever
Mosquito
Africa, Asia
Human diseases Caused by Viruses of the Family
Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distributio
n
Phlebovirus
Phlebovirus
fever
Alenquer
Fever
Unknown
South
America
Naples
Fever
Sand fly
Europe,
Asia, Africa
Rift Valley
Fever
Fever,
encephalitis,
hemorrhagic
fever,
blindness
Mosquito
Africa
Sicilian
Fever
Sand fly
Europe,
Africa, Asia
Human diseases Caused by Viruses of the
Family Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distributio
n
Nairovirus
CrimeanCongo
Nairobi
sheep
disease
CrimeanCongo
hemorrhagic
fever
Hemorrhagic
fever
Tick
Nairobi
sheep
disease
Fever
Tick
Africa, Asia
Africa, Asia
Human diseases Caused by Viruses of the
Family Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distributio
n
Hantavirus
Hataan
Hantaan
HFPS
(hantavirus
pulmonary
syndrom)
Rodent
Asia
Puumala
HFPS
Rodent
Asia
Sequl
HFPS
Rodent
Asia, Europe
Human diseases Caused by Viruses of the Family
Bunyaviridae
Genus and
Group
Virus
Disease
Vector
Distributi
on
Genus unassigned
Bangui
Fever, rash
Unknown
Africa
Bhanja
Fever,
encephalitis
Tick
Africa,
Europa,
Asia
Issk-kul
Fever
Tick
Asia
Kasokero
Fever
Unknown
Africa
Nyando
Fever
Mosquito
Africa
Tataguine
Fever
Mosquito
Africa
Wanowrie
Fever,
hemorrhage
Tick
Middle
East, Asia
FIGURE. Pathogenesis of bunyavirus infections. Humans are
dead-end hosts of most bunyaviruses; however, the blood of Crimean-Congo
hemorrhagic fever patients may be highly infectious.
Signs of Crimean-Congo Hemorrhagic Fever