Viral oncology and retroviruses

Question 1

what is the G1-S checkpoint in the cell cycle

Answer 1

it is mediated by cyclin dependent kinases which target Rb for phosphorylation resulting in dissociation from E2F and transcription of a number of genes including S phase genes, cyclin E and its own expression, driving cells into S phase

Question 2

what are the different types of retrovirus

Answer 2

oncovirus (cancer causing), lentivirus (eg HIV) and spumaviruses

Question 3

describe the retroviral life cycle

Answer 3

the particle has 2 copies of RNA with membrane around it. contents are delivered to the cytoplasm upon binding and fusion. reverse transcriptase makes a copy of retroviral RNA and integrate integrates this into nuclear DNA of the host cell. this is the provirus. this can be assembled into new retroviruses and secreted

Question 4

what are the 3 retroviral genes

Answer 4

gag, pol and env flanked by long terminal repeat sequences (LTRSs) which contain strong promoter and enhancer elements

Question 5

what does Pol code for

Answer 5

proteins which are cleaved by protease

Question 6

what does Env code for

Answer 6

envelope glycoproteins

Question 7

what does Gag code for

Answer 7

proteins which bind to RNA inside the capsid

Question 8

what do complex retorviruses contain in addition to 3 main retroviral genes

Answer 8

non strctural genes which code for proteins which drive replication, virus assembly and other important functions

Question 9

how do retroviruses create space for oncogenes in their genome

Answer 9

sacrifice existing genes eg AMV has a deltion in its env gene to make space for v-myb although this prevents it from replicating efficiently

Question 10

how does avian leucosis virus cause oncogenesis in the absence of a retroviral oncogene

Answer 10

it integrates close to the c-myc gene so the LTRS promoter activates my transcription stimulating cells to enter S phase

Question 11

how is Tax protein in HTLV-1 infected cells oncogenic

Answer 11

it is a transcriptional activator which upreglates cyclins and cyclin dependent kinases as well as E2F and down regulate cell cycle inhibtors. it moduates cell proliferation and stimulates T cell proliferation. cytotoxic t cells are able to recognise and eliminate tax expressing cells however HBZ is transcribed on opposite strand of the provirus which drives proliferation of cells which lose tax expresion and stimulates Treg proliferation