Download DNA viruses: Adeno-, Pox-Papilloma

DNA viruses: Adeno-, PoxPapilloma- and Polyoma Viruses
Foundation Block,
ID#2799
Objectives
• Describe general properties of adeno-, pox-,
papilloma-, and polyomaviruses
• Learn clinical manifestations caused by these
viruses
• Understand the different routes of transmission
of these viruses
• Describe diagnostic approaches
• Understand the principles of prevention and
treatment
Adenoviruses
Adenoviruses
• Description:
• Icosahedral, non-enveloped viruses, double strand
DNA, virion: 70-90 nm, 252 capsomers
• Unique morphological feature (slender fibers)
• Replication in cell nucleus
• First detected from adenoids
• 51 human serotypes
• Seven human subgroup: A-G
• Different serotypes are associated with different
conditions:
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Respiratory (mainly subgroup B and C)
Enteric (subgroup F serotypes 40&41, subgroup G type)
Conjunctivitis (subgroup B and D)
Cystitis (subgroup B)
Adenovirus
• Pathogenesis:
– Infection is usually acquired during childhood
– Transmitted by direct contact, fecal-oral route, and
occasionally waterborne transmission
– Virus multiplies in conjunctiva, nasopharynx, lymph
nodes, intestinal mucosa
– Some types are capable of establishing persistent
asymptomatic infections in tonsils, adenoids, and
intestines and shedding can occur for months or
years in urine or stool
– Some adenoviruses (e.g., serotypes 1, 2, 5, and 6)
have been shown to be endemic in some parts of
the world
Adenovirus
A.Respiratory syndromes
- Account for 5% of RTI
1. Acute febrile pharyngitis
-- Infants, young children
2. Pharyngoconjunctival fever
– Conjunctivitis, fever, pharyngitis and adenoidal enlargement
– Swimming pools
3. Acute respiratory disease
– Military recruits, high morbidity
– Ad4, 7 and 21
– Crowding, repeated exposure to highly infectious doses and
stressful physical exercises
– Fever, malaise, sore throat, hoarseness and cough
4. Pneumonia
Adenovirus
B. Hemorrhagic cystitis:
• Hemorrhagic cystitis is lower urinary tract symptoms
• Caused by Ad11 and 21 of subgroup B
• Infectious
– The most common cause of acute (primary) viral
hemorrhagic cystitis in children (6-15 yrs. old boys)
– Acute dysuria, hematuria and hemorrhage
• Noninfectious in immunosuppressed patients
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Serious complication due to reactivation of latent virus
Asymptomatic hematuria
Urinary retention
Disseminated to other organs may lead to death
Adenovirus
C. Enteric infections (serotype 40,41)
• Adenoviruses account for 4-15% of all
hospitalized children with gastroenteritis
• Fecal oral route
D. Conjunctivitis (subgroup B and D)
• Epidemic keratoconjunctivitis
– Swimming pools
– Aggressive conjunctivitis, pain,
photophobia, lymphadenopathy, keratitis
(inflammation of the cornea) result in
impaired eye vision
Adenovirus
• Treatment
– No antiviral drug
– Supportive and relieving the symptoms
• For respiratory infection include increase fluid
intake, bronchodilator medication and oxygen
supplement
• For enteric include rehydration with water,
mother milk and administration of electrolytes
(orally or by IV fluids)
Adenovirus
• Prevention
– Hand washing
– Wearing gloves
– Avoid public swimming pools
– Vaccine available for acute respiratory
disease which consist of Non-attenuated
live vaccine
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Only for military personnel's not civilians
Packed in enteric capsules
Replicate only in the intestine
Asymptomatic infection
Adenovirus
• Laboratory diagnosis
– Virus isolation
– Immunofluorescent test (IFT)
– ELISA
Poxviruses
• Properties:
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Largest (230-280 nm)
Enveloped
dsDNA viruses
15 enzymes
Cytoplasmic replication
Poxviruses
• Laboratory Diagnosis
– Clinical symptoms
– Antibody detection
– Virus isolation
• Transmission
– Inhalation of infected air droplets or
aerosols
Poxviruses
Classification:
1. Orthopox viruses
1.Variola
2.Vaccinia
3.Cowpox
4.Monkeypox
2. Parapox viruses
1.Orf
2.Pseudocowpox
3. Molluscipoxvirus
Variola
• Is the causative agent of smallpox
• Fever, chills, headaches, nausea, vomiting
and severe muscle pain
• The most characteristic symptom is the
rash
• Macule, papule, vesicles, pustules which
form scares
Smallpox
• During the 18th century killed an
estimated 400,000 in Europe each year
• During the 20th century killed 300-500
million deaths
• In 1950 killed an estimated 50 million
cases
Smallpox
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Eradication of smallpox
Why it was possible?
No animal reservoir
No carrier state
Potent vaccine
Characteristic symptoms
Rare subclinical cases
• In December 1979 WHO certified the
eradication of smallpox
Vaccinia
• Closely related to smallpox
• Mild self limiting disease
• Result in a rash only at the site of
vaccination
• Live vaccinia virus is administered under
the skin
• Protect against smallpox
Cowpox
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Rare
Rates are the natural reservoir
Cows and human are accidental hosts
Resembles smallpox and vaccinia
Localized ulcerating lesion
Self limiting disease
Transmitted by direct contact with the infected
animals during milking
• Protect against smallpox
Poxviruses
• Monkeypox virus
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First identified in monkeys
Prevalent in central and west Africa
Disease resembles smallpox
Transmitted by contact with infected animal blood,
lesion or body fluids
– Transmitted from person to person by infected
respiratory droplets or touching infected body fluids
– Last for 2-4 wks
Monkeypox virus
• Congo 1970-80: 60 cases
1981-86: 400 “
1996-03: >500 “
• Outbreak in US – June, 2003, 71 cases
• Usually infect prairie dogs, squirrels,
imported pets and rodents
Orf (pustular dermatitis)
• The virus can survive for 6 months in the soil
• Transmitted to human by direct or indirect
contact with infected sheep or goats
• The infection result in a single painless solitary
or multiple cutaneous lesions on the hand,
forearm or face
• Lesions heal relatively slow without
complications
• Can lead to a serious eye infection
• Can be treated by cidofovir
Pseudocowpox virus
(milker’s nodules)
• Pseudocowpox is a worldwide disease of cattle.
• Symptoms include ring or horseshoe shaped
scabs on the teats, which usually heal within six
weeks.
• Lesions may also develop on the mouths of
nursing calves.
• Spread is by vomits, including hands, calves'
mouths, and milking machines.
• Lesions appear on the hands of milkers.
Poxviruses
• Molluscipoxvirus
Molluscum contagiosum
• In children transmitted by saliva
– Rash is confined to the face, neck, Palms and
arms, painless
• In adults transmitted sexually
– Rash confined to the genitals, lower Abdomen
and inner thighs
• Self limiting disease (few months to one year)
Papilloma- and Polyoma Viruses
• Papillomaviruses
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Icosahedral, non-enveloped virus
double strand DNA, 70-90 nm
More than100 human types
Not growing in cell cultures
Direct contact
Virion in keratinocytes (horny tissue, brown to grey)
Develop into a typical hyperkeratotic nodules-painless
Latent infection in basal cells
Life cycle of papillomavirus
Papillomaviruses
Clinical manifestations:
1. Cutaneous warts, hyperkeratosis
– Benign lesions on the skin, cauliflower-like surface and are typically
slightly raised above the surrounding skin
– Peak incident in children between 10-14 yrs (swimming pools and
changing rooms)
– Start as flesh colored papules which develop into hyperkeratotic
nodules (painless)
Verruca plana
V. plantaris
V. vulgaris
Papillomavirus
2. Epidermodysplasia verruciformis
– Rare life threatening disease
– Autosomal recessive genetic hereditary skin disorder
associated with a high risk of carcinoma of the skin
– It is characterized by abnormal susceptibility to HPVs
of the skin
– Large proportion of people with the disease are
descendant of related marriages
– They develop wide spread of scaly macules and
papules, particularly on the face, hands and feet
– It is typically associated with HPV types 5 and 8
Papillomavirus
3. Condyloma acuminata (Genital warts)
– Most common benign genital warts in both sex
– Transmitted by sexual contact
– Estimated 450,000 new cases per year
– The highest incident is seen in late teens and early
adulthood
– Infection most often regress spontaneously
– Majority of infections become latent
– Recurrences are common
Papillomavirus
4. Laryngeal papilloma
• Benign tumor
• Rare condition
• Found in both adults and
children
• Result in bad voice and
breathing difficulties
• Should be removed in a
regular basis to prevent
blockage of the
respiratory tract
Papillomaviruses
5. HPV and cervical cancer
(intraepithelial cervical neoplasia; ICN)
– HPV type 16, 18, 31 and 45
– Account for 11% of all cancers in women
and 2% in men
– 200,000 death worldwide per year
– Malignant and premalignant lesions can be
detected by routine cervical screening (PAP
smear)
– DNA detection technique (PCR)
– If detected early the treatment is very successful
Laboratory Diagnosis of HPV
• PAP smear (routine
cervical screening)
• Samples are taken from
the endocervical and/or
vagina
• Cells are fixed and
stained with a special
stain which allow us to
see nuclear and
cytoplasmic details
• Abnormal PAP smear
show changes in cells
like irregular perinuclear
cytoplasmic clearing
• PCR (HPV DNA)
Treatment options for HPV
1. Cryotherapy
– The most commonly used
– Liquid nitrogen to freeze the warts and the surrounding tissues
– Significant pain
– Multiple visits
2. Surgical excision
– Remains one of the options
– Reccurency rate is high
– Secondary infection
3. Laser therapy
– Promising results
– Recurrency rate high
– Costly and require specific skills
– Impractical for wide spread
Treatment options for HPV
4. Cidofovir
– Antiviral drug activated by intracellular enzymes to form an
inhibitor for DNA polymerase
– Showed promising results for cutaneous and genital warts
especially in immunocompromised hosts
5. Cytodestructive therapy
– Salicylic acid trichloroacetic acid
– Side effect include burning erosions, pain, inflammation and
recurrency rate is high
6. Immunomodulators
– Imiquimode and Interferon
– Enhance the immune response by increasing cytokine production
and stimulating CMI to HPV
– Significant reduction of total warts area and recurrency rate is high
– Side effect is mild
Polyomaviruses
• JC virus
• BK virus
• New polyomaviruses:
– KI
– WU
– Merkel cell
JC virus
• Progressive multifocal leukoencephalopathy (PML), also
known as progressive multifocal leukoencephalitis
• Rare and usually fatal viral disease that is characterized
by progressive damage or inflammation of the white
matter of the brain at multiple locations
• It occurs almost exclusively in people with severe
immune deficiency
• It is caused by JC virus, which is normally present and
kept under control by the immune system after a primary
infection.
• Most primary infections are asymptomatic or mild
infection after which the virus remains latent in brain
cells
JC virus
• Symptoms include weakness or paralysis,
vision loss, impaired speech, coma and
death.
• Laboratory diagnosis
– PML is diagnosed by testing for JC virus DNA
in cerebrospinal fluid or in a brain biopsy
specimen.
– Characteristic evidence of the damage
caused by PML in the brain can also be
detected on MRI images.
JC virus
• Treatment
– Alter immunosuppressive drugs according to
the viral load
– Antimalarial drugs
• Mefloquine is an antimalarial drug that can also act
against the JC virus.
• Administration of mefloquine seemed to eliminate
the virus from the patient's body and prevented
further neurological deterioration.
BK virus
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Primary infection usually asymptomatic
Mild respiratory infection or fever
Some cases develop haemorrhagic cystitis
Remains latent in the kidney and urinary tract
Immunosuppressive drugs activate the virus
In transplant patients:
– Haemorrhagic cystitis (inflammation of the bladder
leading to dysuria, hemorrhage and hematuria)
– Ureteric stenosis (abnormal narrowing in blood
vessels
– BKV-associated nephropathy (BKVAN) leading to
graft rejection due to damage in the kidney
BK virus
• Diagnosis is done by the detection of viral
DNA:
• Blood
• Urine
• Biopsy from the kidney
• Treatment
– Stop immunosuppressive drugs
– Immunomodulators to restore CMI
– Cidofovir
Merckel cell Polyomavirus (MCV)
• Merkel cell carcinoma (MCC) which is a rare skin cancer
and highly aggressive.
• Occur more frequently in immunosuppressed patients
• MCC occurs most often on the face, head, and neck.
• It usually appears as a firm, painless, nodule, or tumor.
• These flesh-colored, red, or blue tumors vary in size
from 5 mm to more than 5 cm.
• MCC metastasizes quickly and spreads to other parts of
the body, tending towards the regional lymph nodes.
• The tumor tends to invade underlying subcutaneous fat
and muscle.
• It can also metastasize to the liver, lungs, brain or bones.
Polyomaviruses
• Diagnosis of MCV
– PCR
• Treatment
– Surgical
– Radiotherapy
• Polyomaviruses WU and KI
– Respiratory infections