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Micro (virology) > Tumor viruses/retroviruses > Flashcards

Tumor viruses/retroviruses Flashcards

1
Q

DNA viruses

A

most replicate in the nucleus
this is beneficial because they use the cell’s machinery for DNA replication

most DNA viruses encode their own DNA polymerase

Many DNA viruses must replicate in proliferating cells that are replicating
cellular DNA, so that the cell’s DNA replication machinery is active.
Some DNA viruses induce cell proliferation and can cause cancer.

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2
Q

over expression or an activating mutation of these can cause cancer

A
  • growth factors or receptors for growth factors
  • cytoplasmic signaling proteins (i.e. ras)
  • Nuclear DNA binding proteins (I.e. c-myc)
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3
Q

inhibition or loss of function mutation of these can cause cancer

A
  • nuclear proteins (p53, p16, RB1)
  • cytoplasmic proteins
  • transmembran proteins
  • location unknown
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4
Q

retroviruses

A

most RNA tumor-causing viruses

but note, not all retroviruses are tumor causing viruses

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5
Q

human retroviruses

A 
HTLV-1 and 2: both can cause cancer cancer- adult T cell leukemia (ATL)
HIV-1 and 2 do not directly cause cancer but HIV-1 and HHV8 infection can lead to kapok's sarcome
Human spumavirus (foamy virus) is not associated with cancer
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6
Q

what type of Virus is HCV

A

hepatitis C virus is an RNA virus

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7
Q

DNA viruses that contribute to cancer in humans

A

herpesviruses: EBV and HHV8
papilloma viruses
HBV
Adenoviruses

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8
Q

what does the induction of cancer require

A

many steps
viral infection is only part of the process
other genetic changes are required

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9
Q

Human DNA tumor causing viruses

A
  • EBV- Burkitt’s lymphoma
  • HHV-8
  • HBV,HCV
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10
Q

EBV- burkitt’s lymphoma

A

is a B cell cancer
chromosome translocations activate c-myc oncogene
occurs as a result of hyper proliferation of B cells
this is induced by the virus and results in chromosome instability
also causes nasopharyngeal carcinoma and Hodgkin’s lymphoma (Hodgkin’s disease)- malignant B cells in lymph nodes, often with infiltration of other cells.

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11
Q

HHV-8

A

Kaposi’s sarcoma
virus has several genes that regulate cell growth, including one that degrades Rb
Causes cancer of epithelial cells in HIV+ individuals with AIDS

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12
Q

HBV, HCV

A

hepatocellular carcinoma
HBV- found integrated into chromosomes
HCV not understood, may cause chromosome instability

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13
Q

EBV’s contribution to cancer

A

promotes the proliferation of infected cells and immortalized B cells in culture
understood via several viral genes which help to induce proliferation

contributions from

  • transcription factors
  • mimics of cellular receptors that induce cell activation and proliferation pathways (they are mitogenic)
  • genes which inhibit apoptosis- often increasing Bcl-2 expression
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14
Q

what further promotes tumorigenesis?

A

improper and continuous cell proliferation provides opportunity for other genetic defects to arise

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15
Q

HPV

A 
small dsDNA
naked isosahebral
8kb genome
categorized by type: 118 
categorize by risk of tumors:low, intermediate and high
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16
Q

what does HPV cause

A

warts/papillomas and cancerous tumors
often sexually transmitted
enters by break in the skin and infects basal epithelial cells
warts are an infection of cutaneous epithelium

17
Q

what can an infection of mucosal epithelium of HPV cause

A

can cause cervical carcinoma, a major cause of death in women, especially in developing countries
~500,000 cases of cervical cancer/year worldwide
300,000 deaths
cervical cancer kills ~4,000 in the US each year
Deaths from cervical cancer in US have declined as a result of routine Pap smears and removal of pre-cancerous tissue

18
Q

what HPV types cause 70% of cervical cancer cases

A

16 and 18

19
Q

what is the 2nd most common cancer in women

A

cervical

20
Q

what types cause 90% of genital warts

A

6 and 11

21
Q

how does HPV proliferation occur

A

HPV degraded p53 and pRb tumor suppressor genes through the action of its E6 and E7 proteins
E6 and 7 are oncogenes

22
Q

progression of HPV

A

in stages
early pre-cancerous stage containing cells that grow abnormally called cervical dysplasia or cervical intraepithelial neoplasia
abnormal growth of squamous cells on the surface of the cervix

23
Q

HPV types causing oral squamous papilloma

A

6,11,16

24
Q

HPV vaccine- Gardasil

A

3 dose
against 6,11,16,18
must be given before infection
recommended for females 9-26 and also available for males

viral capsid protein L1 self assembles into virus-like particles
created in the lab and used in the vaccine to elicit protective antibodies
in particular demand among gay men who are at significantly increased risk for genital warts and anal cancer
‘05 study in SanFran found that 95% of HIV infected gay men also tended to have anal HPV infection on which 50% had precancerous HPV-caused lesions

25
Q

HPV vaccine- Cervarix

A

approved for use in females
protects against 16 and 18
protects against 2 HPV strains that are linked to about 70% of cervical cancer cases in the US
doesn’t offer protection against the HPV strains that cause genital warts- 6 and 11

26
Q

Retroviruses

A 
most RNA tumor viruses are retroviruses
not all are tumor viruses
enveloped
\+ssRNA genome
2 copies  of +ssRNA per virion
27
Q

how do retroviruses replicate

A

through a dsDNA intermediate created by a viral RNA-dependent DNA polymerase- this is REVERSE TRANSCRIPTASE
this DNA copy is integrated into the chromosomal DNA and becomes part of the cell and stays with the cell for life

28
Q

Human retroviruses

A 
HTLV-1
HTLV-2
HIV-1
HIV-2
Human spumavirus (foamy virus)
29
Q

retroviral oncogenesis

A

can cause cancer by more than one method

  1. delivery of a viral oncogene (v-onc) into a cell by infection
  2. insertional (integration) oncogenesis
    2a. activation: cellular oncogene by interaction of retrovirus near it. the viral promoter drives improper expression of the cellular oncogene. too much c-onc is made, or it is made in the wrong cells
    2b. inactivation of a tumor suppressor gene by integration of a retrovirus within it. this disrupts the gene
  3. Retroviral transcription factors- HTLV Tax protein is a transcription factor that stimulates replication of infected T cells. HIV Tat protein is a transcription fact that assists HHV-8 induced transformation

Micro (virology) (7 decks)

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