Principles of Viral Oncogenesis

neoplastic

what kind of disease is cancer?

tumor (neoplasm)

a swelling caused by abnormal growth of cells

benign tumor

generally, does not cause harm, stay in primary location with distinct, smooth, regular borders

malignant tumor

damages and impairs normal functions of tissues, invades, metastasis

oncogenesis

mechanisms of the development of cancer

carcinogenesis

complex, multistage process by which a cancer develops

neoplasm

an abnormal new growth

hepatocellular carcinoma

a cancer of liver epithelial cells

leukemia

a cancer of white blood cells

oncogenic

causing a tumor

sarcoma

a cancer of bone and soft (connective) tissue

non-acute transforming retroviruses

Transform via insertion, activation of proto-oncogenes (e.g.,Murine leukemia virus)

acute transforming retroviruses

Carry protooncogenes (v-onc); e.g., Avian sarcoma virus

trans-acting retroviruses

Human T-cell Leukemia Virus (HTLV)

non-acute transforming retroviruses

these are common in nature and involve no human cancers

insert and disrupt gene regulation

mechanisms of non-acute transforming retroviruses?

LTR

contains promoter/enhancer elements - cellular regulatory proteins can bind

promoter insertion

up-regulate cellular gene - if insertion is 5' of gene (+ close)

enhancer activation

LTR enhances transcription in neighboring genes - more common

acute transforming retroviruses

these are uncommon in nature and do not involve human cancers

defective virus (requires a helper virus)

acute transforming viruses are ____ _____

viral oncogene

what do acute transforming retroviruses carry?

C-gene (c-myc)

cellular "proto-oncogene" - performs function, often involved in regulation or signaling

V-gene (v-myc)

viral oncogene - effect on cell regulation, leading to transformation

trans-activating tumor viruses

these are uncommon in nature

viral regulatory proteins on cellular genes

trans-activating tumor viruses action of:

CD4+ lymphocytes

what does HTLV-1 infect?

a subset of lymphocytes

what does HTLV-1 transform?

immortalized T cells

HTLV-1 involves numerous:

aggressive clone is generated (HTLV-1)

Acute adult T-cell leukemia/lymphoma (ATLL) occurs when an

like HIV

how is HTLV-1 transmitted and acquired?

tax

HTLV-1 carries accessory gene ____ which is a transcriptional regulator

promoters

tax activates _____ in viral LTR and cellular genes

LTR

V-oncogene is under transcription control of the:

IL-2

when CD4+ infected with HTLV they become independent of _____ and become immortalized

primary hepatocellular carcinoma (PHC)

what does HCV predispose patients to ?

hepatocytes

HCV persistently infects

liver tissue

HCV causes continual destruction and regeneration of:

cancer

within HCV, there is continual induction of cell growth that may lead to:

HPV

cervical cancer

MCC

Merkel cell carcinoma

hepB

PHC

EBV

B cell lymphoma

HHV-8

kaposi sarcoma

SV40

cancer in animals

myxoma

cancer in animals

Adeno

experimental only

S phase

DNA viruses (most) can push cells into:

S phase genes

What do small DNA viruses induce?

extend it

what do small DNA viruses do to the life of cell?

normal regulatory proteins (tumor suppressor genes)

what do small DNA viruses block the action of?

papillomaviruses

example of small DNA virus?

extracellular gfs or intracellular signaling systems

what do large DNA viruses interact with?

perpetual cellular replication

what do large DNA virus result in?

herpesviruses EBV and HHV-8

example of large DNA viruses?

homologs of cellular genes involved in signaling

what do large DNA virus encode?

tumor suppressor genes

negative regulators of cell growth

deleted or damaged

tumor suppressor genes are often what in cancer cells?

p53

example of tumor suppressor gene?

G1-S

what doe p53 regulate?

benign epithelial overgrowth

what do human papillomaviruses cause?

16, 18, 31

can cause cervical carcinoma?

E6, E7

maintain cells in S phase for virus replication - involved in cell immortalization and transformation

SV40

t antigen - no human cancers

Merkel cell carcinoma

rare aggressive skin cancer - sun exposure - weakened immune system

SV40 and MCC

what are some examples of human polyoma

EBV

gammaherpesvirus - cofactor in carcinogenesis

cells bearing CD21 (B cells)

what cells does EBV infect?

nasal pharyngeal carcinoma - burkitts lymphoma - Hodgkins disease

B cell type cancers associated with EBV?

kaposi sarcoma

neoplasm of the skin and viscera

cancer cells

Fragments of integrated HBV DNA are found in: