DNA Tumor Viruses

Question 1

Introduction

Answer 1

DNA tumor viruses transform only non-permissive cells
Interaction of specific viral proteins with products of tumor suppressor genes directly lead to or contribute to the transformation process
EBV, HBV, HSV, and HPV are associated with human cancers

Question 2

Adenoviruses (normal human virus) SOME cause cancers.

Answer 2

Types
Vary in their oncogenic potential from high to not at all
Types 12, 18 and 31 are highly oncogenic
Transformation characteristics
Transform rodent cells
No association with human neoplasms
Transforming proteins
E1a – binds to p110Rb (represses cell proliferation)
E1b – binds to p53 (represses cell proliferation)

Can make early proteins, but needing others for

Question 3

Papillomaviruses

Answer 3

Types
60 different types have been described; types 16 and 18 have a strong association with cervical intraepithelial neoplasia (CIN)
Transformation characteristics
Majority of cervical, penile and vulvular cancers contain HPV DNA
Suspected cofactors include tobacco smoke and coinfection with HSV
Virus multiplies only in differentiating keratinocytes
Type 16 transforms rodent cells
Viral DNA is episomal in normal tissue, but integrated in cancers and CIN
Transforming proteins
E6 – binds to p53
E7 – binds to p110Rb

Interesting b/c normally cause warts. HPV moves into layers of skin. ONLY when cells differentiate into keratinocytes. Preciding that can cause…

Question 4

Polyomaviruses

Answer 4

Types
BK (renal transplant patient) and JC (PML patient) viruses can transform rodent cells and induce tumors in newborn hamsters
SV-40 replicates in monkey cells, transforms rodent cells and induces tumors in newborn hamsters
Polyoma virus replicates in mouse cells and transforms hamster’s cells
Transforming proteins
SV-40 – large tumor (T) antigen has domains that bind to p110Rb and p53
One or two of the three polyoma virus T antigens have transforming activity

Question 5

Herpesviruses

Answer 5

Some are linked to human cancer
Data is most convincing for EBV
EBV
Linked to Burkitt’s lymphoma and nasopharyngeal carcinoma
EBV DNA in Burkitt’s cells
Viral genome is mostly exists as multiple episomes, but some is integrated into genome
Important viral proteins involved in transformation include: EBNA-2 (transcriptional transactivator…protein that jumps around and can activate transcription), LMP 1 and LMP 2a and b (tyrosine kinases) -these are somehow involved!
Possible cofactors involved are malaria and c-myc proto-oncogene translocation (chromosome 8 to 14)

HSV-2
Implicated in cervical cancer and CIN
DNA fragments, including those containing ribonucleotide reductase, can transform cells
CMV
Implicated in cervical cancer and CIN
Some DNA segments can transform cells
HHV-8 (KSHV; Kaposi’s sarcoma-associated herpes virus)
Cause of Kaposi’s sarcoma
Implicated in multiple myeloma
Contains 16 cellular genes including C-cyclin and cytokines - int’x of these that cause ….to occur

Question 6

Hepadnaviruses

Answer 6

75-85% of primary human hepatocellular carcinoma cells carry human hepatitis B virus (HBV) genes
Impaired immunity and alcohol-associated hepatic cirrhosis are co-factors
X protein interacts with p53
Latency period between infection and primary hepatocellular carcinoma ranges from 9-35 years