Tumor viruses/retroviruses Flashcards
DNA viruses
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.
over expression or an activating mutation of these can cause cancer
- growth factors or receptors for growth factors
- cytoplasmic signaling proteins (i.e. ras)
- Nuclear DNA binding proteins (I.e. c-myc)
inhibition or loss of function mutation of these can cause cancer
- nuclear proteins (p53, p16, RB1)
- cytoplasmic proteins
- transmembran proteins
- location unknown
retroviruses
most RNA tumor-causing viruses
but note, not all retroviruses are tumor causing viruses
human retroviruses
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
what type of Virus is HCV
hepatitis C virus is an RNA virus
DNA viruses that contribute to cancer in humans
herpesviruses: EBV and HHV8
papilloma viruses
HBV
Adenoviruses
what does the induction of cancer require
many steps
viral infection is only part of the process
other genetic changes are required
Human DNA tumor causing viruses
- EBV- Burkitt’s lymphoma
- HHV-8
- HBV,HCV
EBV- burkitt’s lymphoma
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.
HHV-8
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
HBV, HCV
hepatocellular carcinoma
HBV- found integrated into chromosomes
HCV not understood, may cause chromosome instability
EBV’s contribution to cancer
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
what further promotes tumorigenesis?
improper and continuous cell proliferation provides opportunity for other genetic defects to arise
HPV
small dsDNA naked isosahebral 8kb genome categorized by type: 118 categorize by risk of tumors:low, intermediate and high
what does HPV cause
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
what can an infection of mucosal epithelium of HPV cause
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
what HPV types cause 70% of cervical cancer cases
16 and 18
what is the 2nd most common cancer in women
cervical
what types cause 90% of genital warts
6 and 11
how does HPV proliferation occur
HPV degraded p53 and pRb tumor suppressor genes through the action of its E6 and E7 proteins
E6 and 7 are oncogenes
progression of HPV
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
HPV types causing oral squamous papilloma
6,11,16
HPV vaccine- Gardasil
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
HPV vaccine- Cervarix
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
Retroviruses
most RNA tumor viruses are retroviruses not all are tumor viruses enveloped \+ssRNA genome 2 copies of +ssRNA per virion
how do retroviruses replicate
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
Human retroviruses
HTLV-1 HTLV-2 HIV-1 HIV-2 Human spumavirus (foamy virus)
retroviral oncogenesis
can cause cancer by more than one method
- delivery of a viral oncogene (v-onc) into a cell by infection
- 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 - 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
