Week 24 Lecture

outline
Adenovirus
Papilloma Virus
 Adenovirus
introduction
• Isolated in 1953 from human adenoid cell
culture
• Two genera:
– Mastodenovirus affect mammals, 47 serotypes
in human disease
– Aviadenovirus affect birds
• linear dsDNA virus
• naked capsid (resist drying and GIT)
– icosahedral shape with pentons at vertices
• act as VAP, haemagglutinin, toxic to cells, type
specific Ags
• cause wide range of diseases:
– bind same glycoprotein Ig family
receptor as Coxsackie B virus
– mild URI to conjunctivitis, gastroenteritis,
hemorrhagic cystitis
• used as vector for gene therapy
Adenovirus structure
 Adenovirus pathogenesis
• Infect epithelial cells lining
respiratory and enteric organs
• Different serotypes have different
VAPs
– different targets
• Cause:
– lytic infections in mucoepithelial cells
– latent infections in lymphoid/ adenoid
cells, tonsils, Peyer’s patches
• reactivate iff immunosuppressed or co-
infection
– Transforming infections in rodent/
hamster cells only
Adenovirus spread
 Adenovirus immunity
• Abs:
– resolve lytic infections
• protect from re-infection by the same serotype
only
• CMI:
– limit viral spread
• Strategies to evade immune system:
– 1) produce short viral RNA segments that
block activation of INF induced anti-viral
state
– 2) produce a protein that binds MHC-I
• prevents infected cells from being
recognized by cytotoxic T cells
– 3) produce proteins that decrease TNF
induced inflammation
• decrease immuno-pathology
 Adenovirus epidemiology
• Naked capsid
– stable to detergents, drying, poor
chlorine, GIT (acid/ protease/ bile)
• Spread via:
– fecal- oral, fingers, fomites, poorly
chlorinated swimming pools
• Only human to human spread
– no animal vectors
• Most infections are asymptomatic
– increase spread by shedding from
pharnyx and feces
• Increased risk with close contact
– army barracks, classrooms, day care etc.
 Adenovirus clinical
syndromes
• Pharyngitis and
conjunctivitis
• Acute febrile – mostly in older
pharyngitis and children
pharyngconjunc • Pharyngitis
tival fever – children <3 y.o.a.
• Rapid Strep test to
confirm it is NOT
Strep. Throat

• M/C’ly mild URI

with fever,
rhinorrhea and
cough
 Adenovirus clinical
syndromes
• Fever, cough,
• Acute
pharyngitis, cervical
respiratory
lymphadenopathy
disease
– usually in military
recruitment camps

• atypical pneumonia
• Other in kids/ adults
respiratory – laryngitis, croup,
diseases bronchiolitis
• pertussis-like
illness with
prolonged course
 Adenovirus clinical
syndromes
• Conjunctivitis • Inflammation of
and epidemic both palpebral
keratonconjunct and bulbar
ivitis “Shipyard conjunctiva
eye” – mucosa becomes
pebbled
• associated with
swimming
pools, dust/
debris,
contaminated
eyewash first
aide supplies
Adenovirus conjunctivitis
 Adenovirus clinical
syndromes
• Severe diarrhea,
cramping, n/v
• Gastroenteritis – 2nd only to
rotaviruses as
cause of acute
gastroenteritis in
children
• serotypes 40/ 41
– rarely cause fever
or URI
• chronic diarrhea
in HIV/ AIDS
– unknown other
 Adenovirus clinical
syndrome
• Systemic • Less risk than
infection in HSV
immunocomprom – can cause
hepatitis and/ or
ised
pneumonia
• occur either
from exogenous
or endogenous
infection
(reactivated)
• Other diseases • intussusception
in young children,
acute
hemorrhagic
 Adenovirus lab diagnosis
• Sample must be taken from site (eg.
Throat swab) or secretion relevant to
disease (eg. Sputum, feces)
• Culture:
– characteristic CPE after 6-20 days
• Microscopy:
– dark, dense, intranuclear inclusion bodies
in infected epithelial cells
• rare, and similar to Owl’s eye inclusion
body in CMV but no cytomegaly
– electron microscopy of stool sample
• Lab: leukocytosis
• increased CRP (unique to viruses similar
Adenovirus SEM and CPE
Inclusion bodies- Adenovirus vs CMV
 Adenovirus treatment/ control and
gene therapy
• Treatment:
– supportive only
• Control:
– good hygiene
– Vaccines live oral vaccines
• potentially dangerous only for military
personnel
• Gene replacement therapy:
– low pathogenic potential
• use as vectors for treating disease like
CF, lysosomal storage disease,
adenosine deaminase disease, some CA
• eg. CF
– 70% is due to a single gene defect in CFTR
gene
» aerosolized recombinant adenovirus as
gene therapy
» human trials started in 1993- now using
 Human papilloma virus
introduction
• Family Papoviridae
• Genus:
– 1) Papilloma: HPV (>100 types)
• a) cutaneous: verruca (warts)
• b) mucosa: genital, oral, conjunctival
papillomas, cervical CA
– 2) Polyoma
• a) BK/ JC: ubiquitous, M/C’ly asymptomatic or
renal disease or PML
• b) SV40: model oncogene
• small, non-enveloped, circular dsDNA
virus
• defined tissue tropism
– depending on tissue receptors and cell
specific transcriptional machinery
HPV structure
 HPV pathogenesis
• Cause lytic, chronic, latent or
transforming infections
• access basal lamina layer of
squamous epithelium through breaks
in skin and mucosa
• local (non-spreading) persistent
infection
– becomes active as keratinocytes
differentiate (3-4 months)
• usually resolves spontaneously
• Transformation occurs because:
– proteins produced by certain strains (eg.
HPV-16 and HPV-18) bind and inactivate
tumor suppressor molecules like p53 and
p105RB
– cofactors?
HPV pathogenesis
HPV pathogenesis
 HPV epidemiology

• Naked capsid virus

– stable to drying, detergents
• transferred by fomites
– (towels, counter tops, pool decks etc.)
• need direct contact into small
breaks in skin/ mucosa
– also transferred as an STD, infected
birth canal or by chewing warts
Distribution of types of
warts
• Common, plantar and flat
verruca
– M/C in children/ young adults
• laryngeal warts
– M/C in young children and middle
aged adults
• genital warts
– M/C’ly in sexually active females
• but anti-HPV-16 Abs are also found in
virgins and young girls?
 HPV clinical syndromes
• Common flat wart
(verruca plana or
verucca vulgaris)
• M/C on hands and
feet
– keratinized skin
• dome shaped or
flat
– plantar depends on
HPV type and
infected site
• surface is
studded with
 Common flat wart
(verruca plana or verucca vulgaris)

• M/C’ly 3-4 months incubation

– self-limiting and benign
• M/C’ly painless
– but plantar is painful because it
grows inward and is on points of
maximal pressure
• eg. Head of metatarsal bones
 HPV clinical syndromes

• Oral papillomas
– M/C singular,
rarely recur,
incidence at any
age
• pedunculated
with
fibrovascular
stock, rough
papillary
appearance
– increased
incidence if
 HPV clinical syndromes

• Laryngeal
papillomas
– M/C epithelial
tumor in the
larynx
• HPV-6 to HPV-11
• Bimodal incidence
– children < 5
y.o.a. (infected
birth canal) and
adults >15
y.o.a.
(orogenital
contact)
• hoarseness or
abnormal cry
– can be life-
threatening in
children due to
airway
 HPV clinical syndromes
• Condyloma acuminata
(anogenital warts)
– HPV-6 and HPV-11
• rarely progress to CA
in healthy
individuals
• genital warts
– on squamous
epithelium of
cervix, anus,
vagina, urethra,
penis
• transmitted as STD,
vaginal birth or ?
• Often recur after Tx.
– rarely regress
spontaneously
• become larger
 HPV clinical syndromes
• Cervical dysplasia and cervical CA
– 2nd M/C cancer in women in USA, HPV
genome in 90% of cervical neoplasms
• HPV-16 and HPV-18
• progress through 3 stages that can
spontaneously regress at any stage
– Infection CIN-I-observable dysplasia
CIN-II- moderate dysplasia severe
dysplasia or carcinoma
• takes about 1-4 years to progress to CA
• need co-factors to progress to CA
– Eg. smoking, HSV infection, low folic acid,
BCP use, other STDs, multiple sex
partners, young age at 1st intercourse,
low immune status (HIV+, organ transplant,
 HPV lab diagnosis
• Microscopy:
– PAP smear and characteristic histiological
changes (hyperkeratosis, hyperplasia of prickle
cells)
• presence of Koilocytes
– enlarged keratinocytes with clear halos
around shrunken nuclei
• Problem:
– they are not always present, they are not
specific to HPV and they are not helpful in
differentiating between high and low risk of
malignancy
• topical 5% acetic acid
– whitening of epithelium in areas of high
nuclear density (not specific for HPV)
• PCR and DNA probes of cervical-
vaginal squamous epithelial cells
HPV effect on cells
HPV koilocytes
 HPV treatment/ Prevention
• Usually spontaneously regress (months
to years)
• Treatment:
– non-surgical--cryotherapy (liquid N2 etc.),
electrocautery, podophyllin, 2% salicylate,
– Alternative: green banana/ garlic/ onion
poultice, Vitamin E, Chamomile, Tea Tree
oil, lemon oil in apple cider vinegar, Thuja/
Rhus tox etc. homeopathic
– INF therapy, Imiquimod (Aldara) (topical
immune modulator cream), Podofilox
(Juniperus and Podophyllum)
• Prevention:
– safe sex, avoid contact with infected
people, wear sandals in public shower/
 Wart folk remedies
• Some other wart remedies include these:

* Take an equal amount of brown soap and spit, mix the two together, and make a plaster.
Apply it on the warts and leave it 24 hours. When removed, the warts and roots will come
off.

* Make the wart bleed. Put one drop of blood on seven grains of corn. Feed the corn to an
old black hen.

* Tie a human hair around the wart and leave it in place for several days. Remove the hair
and place it in a nail hole in a green tree. Replace the nail, driving it into the hair so it will
be stuck in the tree. When the hair rots, the wart will disappear.

* Put a drop of milkweed juice on a wart or rub a piece of wild turnip on the wart several
times.

* Gather the roots of pokeweed. Fry them in hot grease. Apply the grease to the wart.
After four or five applications, the wart should come off.

* Rub an old bone on the wart and throw it over your shoulder.

* Sit in a cemetery for three nights in a row. Then find a fresh grave and put flowers on it
while wishing that your warts will disappear. Two weeks later, they will.

* Karla Shearer of Houston told us this story: "I had a Cajun friend from Fannett, Texas,
who told me the best way to cure warts was to 'buy them off someone.' She said she'd
had warts as a child and her aunt asked her if she could 'buy them warts.' My friend said
the aunt gave her a quarter for the warts and they were gone in a week." Karla later tried
to buy warts off her daughter, but it did not work. She said she probably jinxed the cure
by first telling her daughter of the story.
 Quote of the day
• If you think you are beaten, you are;
• If you think you dare not, you don’t
• If you like to win and don’t think you can
• It’s almost a cinch you won’t.
• If you think you’ll lose, you’re lost;
• For out in the world, you’ll find
• Success begins with a fellow’s will
• It’s all in the state of mind.
• Anonymous
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