Infectious agents and cancer

Question 1

Rous Sarcoma virus

Answer 1

Oncogene-carrying retrovirus
RNA converted to dsDNA by reverse transcriptase
Provirus integrated into DNA
Induces tumours in days/weeks

Question 2

src oncogene

Answer 2

RSV similar to ALV but with addition of src gene (avian origin)
Viral genome integrated upstream of src gene (c-src)
Replicated with host src to produce v-src (viral copy)
V-src lacks tyrosine-527 so is permanently active

Question 3

c-SRC

Answer 3

Non-receptor tyrosine kinase
Phosphorylated at tyrosine-527 (c-terminal tail) which allows docking of SH2 domain (inactivation)

GF binds SH2. C-terminal tail dephosphorylated, exposing Tyr416 on activation loop

Tyr416 phosphorylation moves activation loop and exposes catalytic cleft (activation). Drives proliferation

Question 4

ALV

Answer 4

Avian leukosis virus
Provirus inserts randomly into host genome
May insert upstream of c-myc (TF)
Virus has strong promoter so myc is overexpressed

Question 5

HPV

Answer 5

Over 150 types. most innocuous (warts)
High risk HPV 16 and 18 cause cervical cancer
Enters skin through micro-abrasion. Infects basal keratinocytes
Maintained as an episome and produces early genes (E6/7)

Question 6

High risk E7

Answer 6

Binds RB (regulates proliferation) and targets it for proteasomal degradation. Allows E2F to bind target genes, leading to proliferation

Also binds RB related proteins

Question 7

High risk E6

Answer 7

Interacts with E6AP ligase stimulating ubiquitination of p53.

Also derepresses hTERT expression (telomerase component) and stimulates VEGF expression (angiogenic factor)

Question 8

Helicobacter pylori

Answer 8

Causes up to 90% of stomach cancers

Chronic inflammation and resultant genotoxic stress drives carcinogenesis

Question 9

CagA virulence factor

Answer 9

Produced by H. pylori
Disrupts cytoskeleton, cell polarity and cell junctions.
Mitogenic
Pro-inflammatory