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10.14 Polyoma and Papillomaviruses
at 10:00 by Dr. Foster
87
Microbiology
Professional
10/15/2011

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Term
Name a few different polyoma viruses.
Definition
SV 40: (vacuolating virus-simian virus), JC virus, BK virus, Merckel cell virus
Term
How similar is JC virus to SV40?
Definition
70%
Term
How similar is BK virus to JC virus?
Definition
80% similar
Term
What disease does BK virus cause?
Definition
hemorrhagic cystitis
Term
What disease does JC virus cause?
Definition
progressive multifocal leukoencephalopathy
Term
What are the similarities between polyoma and papilloma viruses?
Definition
ds circular DNA, replicate in the nucleus, small, non-enveloped virus with icosahedral symmetry
Term
How are polyoma and papilloma viruses different?
Definition
polyoma hvae smaller capsids (45nm versus 55nm), smaller genomes (5,000 bp vs 8,000 bp), different genomic orientation
polyoma has large T transforming protein while papilloma virus has E6/E7
Term
BK virus causes hemorrhagic cystitis classically in what patients?
Definition
organ transplant patients
Term
What are the commonalities between JC and BK viruses?
Definition
acquire infection during childhood, remain latent in kidney (achaetype JC), lymphocytes and brain (JC variant), relapse during severe immune suppression
Term
What is the tropism of JC virus?
Definition
epithelial cells; neurons; oligodendrocytes; astrocytes
Term
What isthe pathogenesis of JC virus?
Definition
the initial site of infection may be the tonsils or GI tract where virus remains latent. Also can infect the tubular epithelial cells in thekidneys where it continues to reproduce shedding virus particles in the urine. JCV can cross the BBB to infect oligodendrocytes and astrocytes
Term
How do you treat JC virus?
Definition
possibly ribavirin and cidofovir
Term
How does JC virus cause PML?
Definition
local demyelination, swollen oligodendrocytes and reactive gliosis
Term
What is the clinical presentation of JC virus PML?
Definition
insidious onset-impaired speech and vision; mental slowness. Progresses in weeks to months to paralysis, blindness, sensory abnormalities, and death
Term
JC virus preferentially infects what type of cell?
Definition
oligodendrocytes
Term
What is the histological apperance of PML?
Definition
demyelination with abundant foamy macrophages and relative preservation of axons. Viral inclusions in enlarged oligodendroglial nuclei.
Term
How do you diagnose JC virus PML?
Definition
suggestive CT/MRI changes; biopsy; PCR for JC virus in CSF
Term
How do you treat JC virus PML?
Definition
ara-C (antiviral/anti-tumor) no good; interferon alpha may be effective; improve immune funciton (HAART)
Term
What drugs put a patient at risk of developing PML via JCV?
Definition
rituximab; efalizumab (raptiva for psoriasis: CD11 antibody)
Term
What is hemorrhagic cystitis?
Definition
diffuse inflammation of the bladder leading to dysuria, hematuria, and hemorrhage
Term
What viruses are associated with hemorrhagic cystitis?
Definition
adenovirus and BK virus
Term
How do you diagnose BK virus hemorrhagic cystitis?
Definition
viral culture, EM, ELISA, PCR
Term
How do you treat BK virus hemorrhagic cystitis?
Definition
non clearly effective (ribavirin??) cidofivir can decrease viuria and comobo of two showed efficacy
Term
What is Merkel cell carcinoma?
Definition
rare and aggressive skn tumor that is usually seen in older caucasians. often located on head or neck and after sun exposure.
Term
What percent of Merkel cell tumors contain MCV?
Definition
80%
Term
How many cases of merkel cell are there in the US each year?
Definition
1500
Term
What are the risk factors for merkel cell carcinoma?
Definition
exposed to natural or artificial sunlight (tanning beds or psoralen and ultraviolet A therapy for psoriasis), having a weakened immune system (chronic lymphocytic leukemia or HIV infection, post-organ transplant)
being older than 50, male or white
Term
How do you diagnose MCC?
Definition
skin biopsy. MCC tumor cells express cytokeratin-20 (a low molecular weight intermediate filament), which shows a characteristic dot like perinuclear pattern in cells. Als o they express MCV LgT
Term
What are the four major treatments for MCC?
Definition
1) surgical excision of primary lesion 2) lymph node removal 3) radiation 4) chemotherapy
Term
T/F All polyomaviruses have a large T antigen that may be involved in cellular transformation.
Definition
true
Term
What strains does gardasil protect against?
Definition
HPV 6, 11, 16, 18
Term
T/F HPV can be routinely grown in the lab.
Definition
false!
Term
HPV 1,2 cause...
Definition
plantar and common warts
Term
HPV 6,11 cause..
Definition
condylomata and laryngeal warts
Term
HPV 16, 18, and others cause...
Definition
anogenital malignancies
Term
How many types of HPV are there?
Definition
100 types
Term
What are the risk factors for women of being infected by HPV?
Definition
young age (20-24), increase sex partners, early age of first sexual intercourse, male partner sexual behavior, smoking, oral contraceptive use, uncircumcised male partner
Term
What are the risk factors for men for HPV infection?
Definition
young age (25-29), number of sex partners, being uncircumcised
Term
What strains cause plantar warts and who gets them?
Definition
1 (2); adolescents and young adults
Term
What strains cause common warts? Who gets them?
Definition
2 (1), school aged children get them. Prevalence is approx 50%
Term
What are flat warts?
Definition
caused by HPV 3,10; verrucous; least common wart
Term
What occupations put you at higher risk for getting HPV 7 warts?
Definition
butchers, meat packers, fish handlers
Term
Over the past 30 years the prevalence of HPV anogenital warts has increased by...
Definition
2-10x
Term
How many people contract HPV anogenital warts each year?
Definition
5.5 million
Term
What percent of people get HPV in their lifetime in the US?
Definition
50%
Term
What percet of cases of HPV anogenital warts spontaneously regresses?
Definition
20%
Term
Where are HPV anogenital warts found?
Definition
on shaft of penis, vulva, or around anus
Term
What strains cause respiratory HPV? What population is at risk?
Definition
6 and 11
pre-school children possibly due to verticle transmission; adolescents and adults from orogenital contact
Term
What are the symptoms of respiratory HPV in preschool children?
Definition
hoarseness, change in cry, stridor (noisy breathing)
Term
Which HPV strains cause oral warts?
Definition
6, 11
Term
What percent of female reproductive tract cancers are associated with HPV?
Definition
cervical (95%), vaginal (50%), and vulvar (>50%)
Term
What percent of penile cancers are due to HPV?
Definition
50%
Term
Wh percent of anal cancers are due to HPV?
Definition
>70%
Term
What percent of orophrayngeal acncers are due to HPV?
Definition
20%
Term
What percent of nonmelanoma skin/cutaneous squameous cell carcinomas are due to HPV?
Definition
90%
Term
What is the mortality of cervical cancer?
Definition
35%
Term
What age group does cervical cancer occur in?
Definition
30-50 yoa
Term
T/F premalignant lesions (CIN) of cervical cancer develop early after infection with HPV.
Definition
true
Term
T/F the number of cases of cervical cancer has declined over the past 40 years.
Definition
true
Term
How common is cervical cancer worldwide?
Definition
2nd most common malignancy worldwide
Term
How does HPV cause cancer?
Definition
E6 of high risk types binds and degrades p53. E7 of high risk types binds and inhibits the function of tumor suprpessor gne Rb
Term
Which cells of the female genital tract do cancer-casing HPV strains infect? How do these cells become cancerous?
Definition
basal epithelial cells of the cervix which migrate and differentiate towards the epihtelial surface where the now squamous cells sstart to express hte late HPV genes. In transformed epithelial cells, HPV genes are integrated into the host chromosomes and express p53 and Rb
Term
How do you diagnose HPV?
Definition
clinically (genital warts, epithelial defects), papsmear/colposcopy/biopsy, DNA hybridization or PCR, detection of antibody against HPV
Term
What are liquid pap smears?
Definition
place cervical brush in liquid to preserve morphology of cells (thin prep, surepath)
Term
What stains are used in classical pap smears?
Definition
haematoxylin, eosin, light green yellow dye that stains cytoplasm of other cells, organ keratin counterstain
Term
What does haematoxylin stain in pap smear?
Definition
nucleus and also imparts yellow color to glycogen
Term
what does eosin stain in pap smear?
Definition
azure; stains superficial epithelial squamous cells, nucleoli, RBCs, and cilia
Term
What are the hallmarks of an abnormal pap smear?
Definition
dyskaryosis, microvaculization, perinuclear clearing
Term
What are the two types of atypical sqamous cells (ASC) as defined under the 2001 bethesda system?
Definition
atyical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude high-grade squamous intraepihtelial lesions (ASC-H)
Term
What are the two types of squamous intraepithelial lesions (SIL) as defined under the 2001 Bethesda system?
Definition
low grade SIL (LSIL); indicative of mild dysplasia, cervical intraepithelial neoplasia 1 (CIN 1)
high grade SIL (HSIL); indicative of moderate and severe dysplasia, CIN 2/3, carcinoma in situ (CIS)
Term
What percent of pap smears are normal and abnormal?
Definition
90% are normal, 7% are equivocal (ASCUS, repeat pap or test for HPV), abnormal 3% (LGSIL: colposcopy with biopsy, HGSIL: colposcopy with biopsy and treat)
Term
What is an acetic acid douche used for on colposcopic biopsy?
Definition
used to visualize abnormal epithelium (enlarged nuclei reflect white light)
Term
What are the three categories of cervical intraepithelial neoplasia?
Definition
CIN 1: mild dysplasia; includes condyloma (anogenital warts)
CIN 2: moderate dysplasia
CIN 3: severe dysplasia, includes CIS
Term
T/F CIN 1 caused by HPV can clear without treatmnet.
Definition
true
Term
Which CIN do you treat?
Definition
CIN 2 and 3 can regress but you should treat them
Term
How often should women get pap smears?
Definition
once very year; if 3 consecutive negative years then once every 3 years
Term
T/F All low grade and high grade WIL need colposcopy and followup.
Definition
true
Term
How do you treat CIN II or CIN III?
Definition
ablative
Term
What is the alternative to gardasil?
Definition
cervarix (bivalent HPV 16 and 18)
Term
Strains 16 and 18 cause what percent of cervical cancer?
Definition
70%
Term
What percent of gential warts do strains 6 and 11 cause?
Definition
90%
Term
T/F You can use gardasil to treat cervical cancer and genital warts.
Definition
false
Term
How do you assemble the HPV vaccine particle?
Definition
L1--> L1 pentamer --> 72 penatmers self assemble into non infectious HPV VLP
Term
What yeast makes the gardasil vaccine?
Definition
saccharomyces cerevisiae
Term
What else is in the gardasil vaccine besides the VLPs?
Definition
amorphous aluminum hydroxyphosphate sulfate is an adjuvant added to the VLPS (224 ug per dose)
Term
What is in a dose of gardasil vaccine?
Definition
.5 mL dose contains HPV types 6/11/16/18 (20/40/40/20 ug L1 protein, respectively)
Term
What is a common side effect of gardasil vaccine?
Definition
fainting (pts should remain seated for 15 minutes afte rthey receive the HPV vaccine)
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