Exam III: Lecture 10 Flashcards by Ashlyn Laidman

Over __% of human cancers are caused by viruses

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What are 5 common viruses that cause cancer?

EBV
HBV
HCV
HTLV I
HPV

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1 in 3 people will suffer from cancer

true

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Cancer can be caused by a huge number of factors damaging the cell and when a critical number or hits have damaged the cell it can get ____

Transformed = cancer

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How did scientist figure out that viruses can induce cancer?

1908 = discovered leukemia in chickens was infectious
1911 = a tumor in chicken caused by a virus. Can induce tumor formation in another chicken by injecting the sercoma of a cancerous chicken
Names Rous Sarcoma Virus

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HBV; family, cancer type, cases/year

Hepatitis B Virus
Hepadnavirus
Hepatocellular (Liver) Cancer
340,000

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HCV; family, cancer type, cases/year

Hepatitis C Virus
Flavivirus
Hepatocellular (Liver) Cancer
195,000

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EBV: family, cancer type, cases/year

Epstien-Barr Virus
Herpesvirus
Burkitt’s, Hodgkin’s, Post transplantation lymphoma Nasopharyngeal carcinoma
113,400

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HPV: family, cancer type, cases/year

Human papilloma virus
Papillomavavirus
Cervical cancer, anal cancer, penis cancer, head and neck carcinoma
561,180

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HTLV I: family, cancer type, cases/year

Human T Lymphotrophic Virus
Retrovirus
Adult T cell leukemia
3,300

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KSHV: family, cancer type, cases/year

Kaposi’s Sarcoma-associated herpes virus
Herpesvirus
Kaposi’s sarcoma, pleural effusion lymphoma
102,000

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HBV: mechanism, oncogene, onc. function

Hepatitus B Virus
Chronic Inflammation
X protein
Molecular-signaling dysregulation inhibition of p53

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HCV: mechanism, oncogene, onc. function

Hep C
Chronic inflammation
unknown

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EBV: mechanism, oncogene, onc. function

Epstein-bar
Oncogenic
LMP-I
Molecular signaling dysregulation of NFkB activation lymphoproliferation

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HPV: mechanism, oncogene, onc. function

Human Papaloma Virus
Oncogenic
E6, E7
Inhibition of p53 and Rb Cell adhesion dysregulation

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HTLV I: mechanism, oncogene, onc. function

Human T Lymphotrophic Virus
Oncogenic
Tax
Molecular signaling dysregulation NFkB activation immortalization

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KSHV: mechanism, oncogene, onc function

Kaposi’s Sarcoma-associated herpes virus
Oncogenic
8 differnent ones (vCyclin)
Cell cycle dysregulation, inhibition of apoptosis, immune evasion, autocrine and paracrine fucntions

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Talk me through the regulation of the cell cycle from G1/S-cyclin to DNA synthesis

G1/S-cyclin > activates G1-Cdk (cyclin dependent kinase) > G1-Cdk phosphylated Rb protien = inactivating it > Active E2F ? S-phase gene trascnription > S-cyclin > Activates S-Cdk > DNA synthesis

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Talk me through the regulation of the cell cycle from mitogen to the production of G1/S cyclin

Mitogen = growth factor binds to TKR (tyrosine kinase receptor) > activated Ras > MAP kinase cascade > activation of gene reculatory protein > immediate early gene expression > Myc = gene regulatory protein&raquo_space;> G1/S cyclin

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Is Ras an oncogene or a tumor supressor?

Oncogene

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Is p53 an oncogene or a tumor suppressor?

Tumor Suppressor

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What are 4 causes for p53 to be in stabilized and active?

Hyperproliferative signals
DNA damage
Telomere shortening
Hypoxia

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What are 3 effects of p53 being stable and active?

Cell cycle arrest
Senescence
Apoptosis

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Talk me through the protection of the cell cycle from DNA damage to Inactivated G1/S /S-Cdk

DNA damage > ATM/ATR activation > Chk1/Chk2 kinase activation > phosphorylation of p53 > p53 is stable and active > p53 acts as a TF > produces p21 > p21 binds to Cdk and inhibits it

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Viruses have devised a variety of ways to activate the cell cycle

true

Why is activating the cell cycle advantageous to the virus?

1. Lead to cell death | 2. Latent and persistant viruses often trigger transformation

Viruses interfere with the signal transduction pathways to _____ oncogenes or to ______ tumor suppressor genes (inactivate/activate)

Activate oncogenes | Inactivate tumor suppressor genes

Viruses can interfere with ______ pathways

Apoptotic

Viruses cause cell death in many organs they infect, this may lead to what?

The activation of cell division in an attempt to heal > expose the cell to a greater possibility of acquiring a transforming mutation

Activation of proteins involved in the cell cycle by the virus may predispose the cell to what?

continue cycling the cell in an uncontrolled manner leading to tumor formation

Tell me a story about Epstein-Barr virus

Denis Burkitt > described a cancer found in children in Uganda, East Afria = developed tumors in the jaw which grew rapidly and killed them in a manner of months > restricted to some villages but not other = Epstein said "this must be the work of a virus" > Epstian and barr biopsy the tumors and grow them in culture > found virus = EBV

How many people have Epstein-Barr infections?

90%

What was the eventual answer to why Burkitt's lymphoma only appeared in some areas of Africa?

A chromosomal translocation which activated c-myc oncogene is required before the virus can transform the cell The chomosomal translocation happened and some point and then the decendents spread through diffrenent parts of Africa

What is the very general mechanism of EBV?

EBV infects B cells and establishes a latent infection

A limited set of _______ are expressed with no production of _______ virus when EBV is latent

Viral Genes | Progeny virus

What genes are expressed during latency of EBV?

1. EBNA 2. EBER (EBV-encoded RNA) 3. LMP

How does overexpression of c-myc predispose people to cancer?

B + T cells have increased rates of recombination > sometimes you get a strong enhancer infront of c-myc > overproduction of c-myc = oncogene > cancerous cell

What does EBNA-1 do?

binds to viral DNA and maintians it as an episome

What does LMP-1 do?

Inserts into the membrane of the B cell > acts as a mitogen receptor > stimulates cell division

What does EBNA, EBER, and LMP do as a whole?

Downregulate the expression of HLA-I and immunogenic EBV proteins

How does the downregulation of the expression of HLA-I and immunogenic EBV proteins help the virus?

It helps EBV evade the immune system HLA-I presents viral peptides to T cells Immunogenic EBV proteins = trigger the immune system

Nasopharylgeal carcinoma (NPC) is endemic in what population?

Southern Chinese

A strong association between NPC risk and ______ on chromosome ___ has been identified

HLA locus on chromosome 6p

How does NPC risk due to HLA locus on chromosome 6p relate to EBV?

There is a link between the presentation of EBV antigens to host immune cells and NPC risk

EBV infection in NPC is ____ in origin, suggesting that NPC develops from what?

Clonal origin | NPC develops from the clonal expansion of a single EBV-infected cell

HPV expresses what two key proteins when transforming?

E6 and E7

What does E7 do?

binds to Rb, p107, cyclin A, B-myb

What does E6 do?

Binds to p53 and induces its degradation

What does E5 do?

It is a part of BPV which binds to PDGF (growth factor) receptor > dimerization and activation

What two key proteins does adenovirus express during transformation?

E1A | E1B

What does E1A do?

Binds to cell cycle proteins such as Rb and p107

What does E1B do?

Binds to and inhibits p53

What does SV40 express during transformation?

Large T antigen

What does Tag do?

Binds to Rb and p53 and inhibits both

RNA viruses bring in oncogenes and integrate them randomly into the genome

True

Retroviruses can carry oncogenes (_____) that were growth regulatory genes picked up from the host cell (____)

v-onc | c-onc

What is the functional difference between a v-onc and a c-onc?

none??

When a retrovirus containing an oncogene infects a cell, it can induce what?

Transformation

How do retroviruses have their genome replicated? What is the implication of this?

By inserting into the host genome | Insertion occurs randomly and may disrupt host genes

The site of insertion can determine the fate of the cell. What are the 3 ways a v-onc can insert itself?

1. In the middle of a tumor suppressor gene (Rb) it will inactivate it = insertional inactivation 2. If it inserts upstream of an oncogene, it can result in the overexpression of the oncogene and subsequent transformation 3. In a way that is not harmful to the cell

Retrovirus insertion is especially bad because it includes what?

Enhancers, promoters, polyadenylation signals, exon signals, etc

What increases the odds that a retrovirus will insert into the genome at a oncogene/tumor suppressor gene?

These genes are being transcribed by the cell > the chromosome is in euchromatin state = more lose so it is easier for virus to insert its DNA

Rb, P21, P53 are common what?

Tumor Supressor

E2F, Cdk are common what?

Oncogenes

What may lead to the formation of tumors in immune-suppressed individuals?

Persistent viruses that are normally controlled by the immune system may be activated when the immune system is failing. The viruses which are normally not dangerous, go on to transform cells.