Viruses In Cancer Flashcards
Characteristics of viruses
Variety of structure and complexity Genetic material RNA and DNA protein capsid membrane envelope Cannot reproduce independently of host cell
What are the host cell functions required in viruses
Viruses cannot reproduce independently of the host cell
Translation of viral mRNA
Genome transcription
Genome replication
- some viruses contain factors to replicate their own genome
- some viruses are completely reliant on the host to replicate their genome
How does a virus cause cancer
Not the viruses intent
Cancer is a side effect of the virus wanting to create new copies of itself which can cause genetic changes to the hosts genome.
Viruses are one of the ways host genome can change along with lifestyle factors, exposure and replicative errors etc.
What are the biological agents classed as carcinogenic to humans
Epstein Barr virus: Nasopharyngeal carcinoma Burkitts lymphoma Immune suppression related non-Hodgkin lymphoma Extranodal NK/T cell lymphoma Hogkins lymphoma Gastric carcinoma Hep B: Hepatocellular carcinoma Hep c: Hepatocellular carcinoma Kaposi sarcoma herpes virus: Prevalent in HIV infected individuals Primary effusion lymphoma Human Tcell lymphotropic virus type 1 Adult T cell leukaemia and lymphoma HIV Non Hodgkin lymphoma Hogkins lymphoma Cervical cancer Anal cancer Conjunctiva cancer -> this virus does not cause the cancer itself but are more prevalent due to the immune deficiency HPV - cervix, vulva, vagina, penis, anus oropharngeal tract Bacteria - Helicobacter pylori
Establishing causality
Difficult to establish because
Have a long latency period between primary infection with virus and tumour
Only small % of virus infected individuals develop the tumour EBV and glandular fever
Complex multi step pathogenesis EBV and nasopharyngeal carcinoma
Virus infection is one link in a chain -> hep c immune mediated inflammation
No experimental animal models for human cancer
HPV and cervical cancer
HPV 16
Immortalisation: normally cells divide and die if this virus is in the cell they will divide indefinitely and not die
Transformation: although cells are immortal these genes alone are not sufficient to cause the host cells to become malignant - further genetic mutations needs to occur in the cells DNA for it to become cancerous
HPV precedes the development of cervical cancer
HPV infection -> 1 decade latency period -> cervical cancer develops
Kaposis sarcoma
Classic
Affects elderly Mediterranean men, patches that spread and coalesce to form nodules or plaques
Iatrogenic
Immune suppression drugs - usually only effects the skin but can effect muscles membranes
AIDS associated -epidemic.
Lesions in many areas of the body au affect many organs
Endemic -
Equatorial Africa population - similar to classic but younger age can include lymph nodes and other organs
Kaposi sarcoma and HIV
More common in those with HIV
Also more common in homosexual men with HIV compared to HIV acquired elsewhere
Also common in women whose partners are bisexual
Kaposis sarcoma and primary effusion lymphoma
Patients constantly show elevated anti- KSHV Antibodies which suggests the virus is replicating
Tumors regularly show DNA and proteins on the virus
Criteria for establishing that some viruses cause cancer
1) the regular presence and persistence of the respective viral DNA in tumour biopsies and cell lines derived from the same tumour type
2) the demonstration of growth promoting activity of specific viral genes or virus modified host cell genes in tissue culture systems or in suitable animal studies
3) the demonstration that the malignant phenotype (tumour) depends on the continuous expression of viral oncogenes or on the modification of host cell genes containing viral sequences
4) epidemiological evidence that the respective virus infection represents a major risk factor for cancer development
Direct carcinogens
Introduction of a viral oncogene into the host cell causes cancer
Indirect carcinogens
Infection causes induction of chronic inflammation - hep c virus
Prevent apoptosis
Virus induced immunosuppression activates other tumour types
HPV infects which cells and how
Needs cells which are still replicating so infects the basal cells
And it does this when the cells in the higher layers are damaged
What does HPV do
E7 which activates the s phase by preventing the action of pRb pushing the cell cycle forward
This activates p53
Also produced is E6 which inactivates p53 inhibiting apoptosis no DNA repair or cell death
What do HPV E6 and 7 do
They cause chromosomal instability
Their expression causes continuous cell proliferation
Loss of p53 mediated DNA repair pathway
Accumulation of chromosomal mutations that eventually lead to cancer
