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