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Virology 06 Human Papillomaviruses and other DNA Tumor viruses*


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In vivo, papilloma virus replication is linked to the differentiation of what
The infected squamous epithelium
What is notable about the HPV genome?
It contains several open reading frames, all on the same strand
How is HPV transmitted
By direct skin contact or sexual contact
HPV is linked to which cancer(s)?
Human cervical carcinoma and ano-genital cancers
HPV is highly restricted in its tissue tropism and replicates only in:
Epithelial cells (skin and mucous membranes)
How is HPV’s double-stranded covalently closed circular DNA maintained?
In an episomal state in relatively low copies in undifferentiated dividing basal cells where early genes are expressed
Which two early HPV genes were stressed in class?
E6 and E7
HPV proteins E6 and E7 do what?
They target tumor suppressor gene products p53 (E6) and Rb (E7) and control entry into the G1/S phase of the cell cycle.
They also stimulate cell proliferation by activating cyclins A and E
Why is HPV very difficult to grow in vitro?
Terminally differentiated keratinocytes are difficult to maintain in culture
In HPV, what only occurs in terminally differentiated keratinocytes?
Late gene products and lytic DNA replication occur only in terminally differentiated keratinocytes
What does a Papilloma result from?
Dysregulated proliferation of basal cells
HPV 6 and 11 infect mucosal epithelia and are associated with:
Condylomata acuminata of the genital tract
The most common HPV types (types 1, 2, 3 and 4) are associated with what
They infect keratinized surfaces, especially on the hands (2, 4) and feet (1), causing common warts. Also Flat warts (3, 10).
HPV 5 and 8 (and, less commonly, HPV 14) are associated with what
Epidermodysplasia verruciformis, an autosomal recessive immunodeficiency with disseminated warts
HPV 6 and 11 are associated with what
They infect mucosal epithelia and are associated with condylomata acuminata of the genital tract
Respiratory papillomatosis is associated with what
Oral and/or laryngeal papilloma caused by HPV 6 and 11, obstructing the airway
Found in young children infected during delivery
HPV 16 and 18 are associated with what
They are associated with cervical intraepithelial neoplasias (CIN) or with invasive carcinoma, high grade dysplasias and carcinomas
What test has decreased incidence of cervical cancer?
Pap smear
Name three members of the Polyoma virus family
What is BKV associated with
Persists in kidney, associated with hemorrhagic cystitis, ureteral stenosis, and some urinary tract illnesses
What is JCV associated with
Progressive multifocal leukoencephalopathy (PML) in immune-compromised individuals and advanced disseminated malignancies
Describe progressive multifocal leukoencephalopathy (PML)
A subacute demyelinating disease in immunocompromised individuals and a common infection of early childhood that affects white matter.
Multiple neurological symptoms
Caused by JC virus
What does progressive multifocal leukoencephalopathy result in
Impairments to speech, vision, coordination, paralysis of the limbs, death
Is the CSF normal in PML?
Yes, the CSF is normal in PML
If monkeys knew anything about micro, they would avoid SV40 T-antigen because:
SV40 T-antigen inactivates monkey p53 and pRb
Monkeys should avoid SV40 t-antigen since
SV t-antigen binds and inhibits monkey PP2A
Describe the most consistent genetic abnormality in Burkitt’s lymphoma
Translocation of c-myc from chromosome 8 to the immunoglobulin heavy chain (IgH) locus on chromosome 14 in human Burkitt’s lymphomas.
Where is Nasopharyngeal carcinoma prevalent?
Southern China
Which protein is relevant to Nasopharyngeal carcinoma?
Latent Membrane Protein 1
What does Latent Membrane Protein 1 in EBV do?
It is an integral membrane protein that interacts with cellular signaling proteins TNF and receptor associated factors (TRAFs) to cause cellular activation

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