Viruses and Human Cancers

Question 1

characteristics of virally transformed cells

Answer 1

viral DNA sequences present - integrated or episomal forms

greater growth potential in vitro - divided indefinitely, higher cloning efficiency, anchorage independents

chromosomal abnormalities - virus expressed “tumor” antigens

Question 2

human viral that can cause cancer

Answer 2

papillomavirusess (HPV)

epstein-barr virus (EBV)

human herpesvirus 8 (HHV)

human T-cell lymphotrophic virus (HTLV-1)

hepatitis B and C (HBV and HCV)

Question 3

papilloma virus (HPV) and cancer

Answer 3

carcinomas, especially cervical and other genital carcinomas

small DNA virus

naked icosohedron, 8000 bp genome

over 200 known types

infects basal epithelia

genital infections are sexually tansmitted, most commonly sexually transmitted viral infection

about 2/3 of young adults acquire HPV of genital tract during first two years of sexual activity

virus induces proliferation of cells in the basal layer, by expression of a subset of viral genes such as E6 and E7

Question 4

Epstein-Barr virus (EBV) and cancer

Answer 4

Burkitt’s lymphoma, nasopharyngeal carcinoma, B cell lymphomas in immunodeficient individuals

large linear DNA virus encoding about 100 genes

viral DNA can be replicated by cell polymerase in non-permissive cells and is replicated by a virus-encoded polymerase in permissive cells

probably only two major types of EBV with similar biology

Question 5

human T-cell lymphotrophic virus (HTLV) and cancer

Answer 5

adult T cell lymphoma

viral genome is RNA, which is copied into DNA by viral reverse transcriptase, and the DNA is integrated into the cell genome

the infected cell is genetically altered irreversibly by the integration event

infects T lymphocytes, integrated viral genome can express viral regulatory proteins that induce cell proliferation

infections have been associated with certain chronic neurological diseases as well

incubation period of 30 to 40 years

transmitted by blood and sexual contact

Question 6

Hepatitis B and C viruses (HBV and HCV) and cancer

Answer 6

primary hepatocellular carcinoma

Question 7

Human herpesvirus 8 and cancer

Answer 7

Kaposi’s sarcoma, body cavity based B cell lymphoma

induces cytokine production, can lead to cell proliferation and malignant transformation

infection of epithelial cells can also give rise to squamous cell carcinoma

Question 8

Gardasil

Answer 8

HPV vaccine

contains recombinant virus-like particles

no viral DNA but trigger antibody response

protects against HPV 16 and 18 plus HPV 6 and 11

only 70% cervical cancer cases

no effect on existing HPV infections

no effect against ~30% of infections that can lead to cervical cancer

Question 9

pap smear

Answer 9

look for changes in nuclei size in cells obtained from the cervix

HPV cells have large nuclei

Question 10

colposcopy

Answer 10

look at the cerviz after an application of 3-5% acetic acid solution, infected cells turn into a light color

Question 11

EBV pathogenesis

Answer 11

transmitted by saliva, infects epithelial cells of the oropharynx

B lymphocytes also become infected and are induce to proliferate

in normal individuals, the proliferating B cells provoke a brisk T cell response

acute disease cased by EBV infection is infectious mononucleosis

polyclonal B cell lymphomas in immunocompromised individuals

in certain regions of the world, EBV infection is associated with Burkitt’s lymphoma

viral genome usually remains episomal in latently infected B cells and in cancer cells

Question 12

LMP1 and LMP2

Answer 12

LMP1 - viral transforming protein, allows entry into B cells through interactions with the CD40 receptor

LMP2 - blocks B cells, allows for hyperproliferation

Question 13

Burkitt’s Lymphoma

Answer 13

genetic instability, chromosomal rearrangement is the cause of the cancer

translocation of c-myc from normal location on chromosome 8 to a location where the antibody heavy chains are being expressed

Question 14

HTLV oncogenic proteins

Answer 14

tax and rex

similar to HIV tat and rev

mechanism of oncogenicity is unclear

Question 15

Hepatitis B virus pathogenesis

Answer 15

hepadnavirus family

genome encodes few genes, relies on cell RNA polymerase to transcription and its own reverse transcriptase to produce progeny viral DNA from RNA

integration of DNA is not ar egular feature

route of infection is by transfusion or sexual intercourse, hepatocytes are important targets for infection

liver dmmage primarily from immune resonse

immune responses are often not able to eliminate the virus

chronic infection and inflammation associated with the development of primary hepatocellular carcinoma

typically 30 years between primary infection and appearance of HCC

Question 16

Hepatitis C virus pathogenesis (flavivirus family)

Answer 16

single stranded RNA virus that encodes its own polymerase

virus is totally different from HBV

HCV viral proteins expressed as a single polyprotein which is cleaved by proteases into individual functional proteins

persistent infection leads to cirrhosis and hepatocellular carcinoma

major route of infection is from contaminated blood transfusions or shared needles

combined interferon and ribavirin therapy can clear persistent HCV in 43% of patients

unclear if can be transmitted by sexual intercourse

Question 17

Merkel Cell Virus

Answer 17

leads to merkel cell carcinoma, rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin