Download DNA-viruses

M. Tvorko
The Herpesviruses
• All members show latency and cause recurrent infection
– more severe with advancing age, cancer chemotherapy, or other
conditions that compromise the immune defenses
• Large enveloped icosahedral dsDNA
• Replicates within nucleus
Herpesviridae
• large Family; 8 infect humans
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–
–
–
–
–
–
–
HSV-1
HSV-2
VZV
CMV
EBV
HHV-6
HHV-7
HHV-8
Epidemiology of Herpes Simplex Viruses
• Transmission
– direct exposure to secretions
containing the virus
– active lesions most significant
source
– genital herpes can be
transmitted in the absence of
lesions
• HSV multiplies in sensory
neurons, moves to ganglia
– HSV-1 enters 5th cranial nerve
– HSV-2 enters lumbosacral
spinal nerve trunk ganglia
Epidemiology of Herpes Simplex Viruses
• Recurrent infection
triggered by various
stimuli
– fever, UV radiation, stress,
mechanical injury
• Newly formed viruses
migrate to body surface
– produce a local skin or
membrane lesion
Type 1 Herpes Simplex (HSV – 1)
• Herpes labialis
– fever blisters, cold sores
– most common recurrent HSV-1
infection
– vesicles occur on mucocutaneous
junction of lips or adjacent skin
– itching and tingling prior to vesicle
formation
– lesion crusts over in 2-3 days and heals
• Herpetic gingivostomatitis
– infection of oropharynx in young
children
– fever, sore throat, swollen lymph nodes
• Herpetic keratitis
– ocular herpes
Type 2 Herpes Simplex (HSV – 2)
• Genital herpes
– herpes genitalia
– starts with malaise, anorexia, fever,
and bilateral swelling and
tenderness in the groin
– clusters of sensitive vesicles on the
genitalia, perineum, and buttocks
– urethritis, painful urination
• Recurrent bouts usually less
severe
– triggered by menstruation, stress,
and concurrent bacterial infection
Herpes of the Newborn
• HSV-1 and HSV-2
• Potentially fatal in the neonate
and fetus
• Infant contaminated by mother
before or during birth
• hand transmission by mother
to infant
• Infection of mouth, skin, eyes,
CNS
• Preventative screening of
pregnant women
– delivery by C-section if
outbreak at the time of birth
Diagnosis, Treatment, and Control
• Vesicles and exudate are typical diagnostic
symptoms
• scrapings from base of lesions showing giant cells
– culture and specific tests for diagnosing severe or
disseminated HSV
• direct fluorescent antibody tests
• Treatment
– acyclovir, famciclovir, valacyclovir; topical medications
Varicella-Zoster Virus (VZV)
• virus enters neurons & remains latent
• later reactivation of the virus results in shingles
with vesicles localized to distinctive areas
– dermatomes
• treatment
– acyclovir, famciclovir, interferon
• live attenuated vaccine
Epstein-Barr Virus (EBV)
• HSV-4
• infects lymphoid tissue & salivary glands
• transmission
– direct oral contact & contamination with saliva
• by mid-life 90-95% of all people are infected
• causes mononucleosis
– sore throat, high fever, cervical lymphadenopathy
• Complications include:
–
–
–
–
heart defects
facial paralysis
rupture of the spleen
jaundice (hepatitis)
Epstein-Barr Virus (EBV)
• 30-50 day incubation
• most cases asymptomatic
• Burkitt’s lymphoma
– associated with chronic coinfections with malaria
• nasopharyngeal
carcinoma in Chinese &
African men
Human Herpes Virus 6
• HHV-6
• T-lymphotropic virus
• transmitted by close
contact
• very common
• causes roseola
– an acute febrile disease in
babies 2-12 months
• can cause encephalitis,
cancer
Human Herpes Virus 6
• begins with fever, followed by a faint
maculopapular rash
• usually self-limited
• adults may get mono-like symptoms,
lymphadenopathy, hepatitis
• over 70% of MS patients show signs of
infection
Diseases of the Skin Caused by Herpesviruses
HEPATITIS B VIRUS:
HEPATITIS B VIRUS:
HBV SPREAD MAINLY BY
PARENTERAL ROUTE
•
DIRECT PERCUTANEOUS INOCULATION OF
INFECTED SERUM OR PLASMA
• INDIRECTLY THROUGH CUTS OR ABRASIONS
• ABSORPTION THROUGH MUCOSAL SURFACES
• ABSORPTION OF OTHER INFECTIOUS
SECRETIONS (SALIVA OR SEMEN DURING SEX)
HBV SPREAD MAINLY BY
PARENTERAL ROUTE
•
POSSIBLE TRANSFER VIA INANIMATE
ENVIRONMENTAL SURFACES
• VERTICAL TRANSMISSION SOON AFTER
CHILDBIRTH (TRANSPLACENTAL TRANSFER
RARE)
• CLOSE, INTIMATE CONTACT WITH AN
INFECTED PERSON
WHO IS AT GREATEST RISK FOR
HBV INFECTION?
• LAB PERSONNEL WORKING WITH
BLOOD PRODUCTS
• SEXUALLY ACTIVE HOMOSEXUALS
• PERSONS WITH MULTIPLE AND
FREQUENT SEX CONTACTS
• MEDICAL/DENTAL PERSONNEL
HBV - Diagnosis
Acute Infection
HBV DNA
HBeAg
Anti-HBe
Anti-HBs
AntiHBc
HBsAg
0
Anti-HBc
IgM
2
Months
4
6
Years
HBV - Vaccine
Vaccine
Engerix-B
Recombivax HB
(Optional 2-dose)
Age Group
Dose
Volume
# Doses
(ug)
(ml)
0-19 yr
 20 yr
Adults on
hemodialysis
10
20
0.5
1.0
3 (mo 0,1,6)
3 (mo 0,1,6)
40
2.0
4 (mo 0,1,2,6)
0-19 yr
 20 yr
11-15 yr
Adults on
hemodialysis
5
10
10
0.5
1.0
1.0
3 (mo 0,1,6)
3 (mo 0,1,6)
2 (mo 0, 4-6)
40
1.0*
3 (mo 0,1,6)
Adenoviruses
1949. Enders et al.: first cell cultures for cultivation of polioviruses
1953. Rowe et al.: removed tonsills for tissue culture
„blind” passages
cytopathic effect (roundish cells)
normal (healthy) cell culture
AD (Adenoid Degeneration)
APC (Adenoidal-PharygealConjuctival)
ARD (Acute Respiratory Disease)
RI (Respiratory Illness)
ADENOVIRUS (1956)
adenovirus
virions
• nonenveloped, ds DNA
• 30 types associated with human
disease
• infect lymphoid tissue, respiratory &
intestinal epithelia & conjunctiva
• oncogenic in animals, not in humans
• spread by respiratory & ocular
secretions
• causes colds, pharyngitis,
conjunctivitis, keratoconjunctivitis,
acute hemorrhagic cystitis
• inactivated polyvalent vaccine
• Inclusion bodies
VIRION: icosahedral, 80-90 nm
252 capsomers: 12 fibers at the
vertices, 240 hexons,
12 structural proteins (polypeptides)
NUCLEIC ACID: ds DNA
REPLICATION in cytoplasm, virion assembly in the nucleus
CLASSIFICATION OF ADENOVIIRUSES
Genera:
Aviadenovirus (birds),
Ataadenovirus (reptiles, ruminants, birds, brush-tail
possum)
Siadenovirus (frog, birds)
Ichtadenovirus (new, fish)
MASTADENOVIRUS (vertebrates animals: more than 100
serotypes, 52 human serotypes)
MASTADENOVIRUS GENUS
Groups (previosly: Subgenera, grouping based on lenght of
fiber, G/C content of DNA, agglutination of red blood cells (HA),
oncogenicity)
A highly oncogenic (types 12, 18, 31)
B weekly oncogenic (types 3,7, 11, 14,16,
21, 34, 35, 51)
C cell transformation in tissue culture
(types 1, 2, 5, 6)
D cell transformation in tissue culture
(types 8-10, 13, 15, 17, 19, 20,
22-30, 32, 33, 36-39, 42-50)
E none (type 4)
F ? (types 40, 41)
G (new group) ? (type 52)
DISEASES CAUSED BY ADENOVIRUSES
DIFFERENT SEROTYPES - SAME DISEASE
SAME SEROTYPE - DIFFERENT DISEASES
RESPIRATORY TRACT INFECTIONS:
pharyngitis: types 1,2,3,5,7,
acute respiratory disease of recruits: types 4,
7,14, 21
pharyngoconjunctival fever: types 3,7
pneumonia: 1,2,3,7
pertussis-like syndrome: type 5
EYE INFECTIONS :
pharyngoconjunctival fever (conjunctivitis),
epidemic keratoconjunctivitis: types 8,19,37
(swimming pool, nosocomial: eye
droplets,
tonometer) in all age group
follicular conjunctivitis: 3,4,11
ENTERIC INFECTIONS: second in
causative agents causing
gastroenteritis in infants (AV types 40, 41,
the first one is rotavirus) and AV type 53 in
adults
diagnozis: EM, ELISA or latex agglutination
Urinary tract infections: acute haemorrhagic cystitis:
types 11, 21 (children, young adults)
INFECTIONS IN IMMUNO-COMPROMISED PATIENTS: encephalitis,
pneumonia, gastroenteritis, generalized disease (type 5 and new
serotypes: 34, 35)
(PREVENTION: „live” adenovirus serotypes 4 and 7 in enterosolvent
capsule)
RECOMBINANT ADENOVIRUSES (GENE THERAPY)
DNA
Introduction of foreign genes
(malignant diseases, diseases
based on gene defects)
immune therapy (cytokin
genes),
moleculare therapy (tumor
suppressor genes),
virus therapy
PARVOVIRUSES
Parvus: very small
VIRION: icosahedral, 20-25 nm
NUCLEIC ACID: (-) DNA
REPLICATION: in the nucleus, with
the help of cellular enzymes
CLASSIFICATION:
Family: PARVOVIRIDAE
Subfamily: PARVOVIRINAE
Genera:
ERYTRHOVIRUS (B19)
Bocavirus (human bocavirus)
Parvovirus (RA-1)
Dependovirus (requires helper virus :
AAV, Adenovirus Associated Virus)
Densovirus (animal pathogens)
adenovirus
AAV
ERYTHEMA IINFECTIIOSUM
„FIIFTH DIISEASE”
(morbiillllii,, chiickenpox,, rubelllla,, scarllet fever )
• Human parvovirus B19 (respiratory
droplets, seasonality: autumn,
winter, high % of seropositivity)
• special affinity to red blood cells
(haematological changes)
• severe situation in chronic anaemia
• in pregnancy: spontaneous abortion,
malformations
Papillomavirus
• papilloma
– benign, squamous epithelial growth,
wart or verruca
• caused by 100 different strains of
HPV
• common seed warts
– Fingers
• plantar warts
– soles of feet
• genital warts
– prevalent STD
• transmissible through direct
contact or contaminated fomites
• Incubation
– 2 weeks – more than a year
Genital Warts
• most common STD in US
• over 6 M new cases each year
• 30 M carriers of one of the 5 types of HPV
associated with genital warts
• strong association with cervical & penile cancer
– type 16 & 18
• Treatment
– podophyllin chemical treatment, cauterization,
freezing, laser surgery, immunotherapy