Tumor Virus Flashcards
Replication of SV40
“ T-antigen recognizes the start site for SV40 DNA replication (origin of replication) and binds to it. Host DNA-directed DNA polymerase then binds to T-antigen and starts viral DNA replication.”
“Capsid proteins self-assemble and package the viral DNA”
t-antigen also binds to inactivate tumor repressor genes
Structure of Papovirus
“small, naked, icosahedral viruses with a double-stranded, circular DNA genome [< 10 kilobases]”
“relies greatly on host proteins (such as DNA polymerase and RNA polymerase) for replication and gene expression”
HPV and tumorigenesis
“HPV is responsible for benign tumors, called papillomas, including plantar and genital warts (condylomata acuminata)”
Strong association with cervical carcinoma
“Two HPV oncogenes have been identified, the early genes E6 and E7, which bind tumor suppressor gene”
Treatment and prevention of HPV
Prevention: safe sex
Vaccination: “A recombinant vaccine has been developed and is now licensed for pediatric use. It is based on viral capsid proteins expressed in yeast”
Adenovirus and tumorigenesis
“Although adenoviruses are not associated with tumors in humans, some can cause tumors in hamsters and transform rat cells in vitro.”
“E1 binds to the tumor suppressor proteins Rb, p300 and CBP. It also binds to cellular transcription factors to stimulate transcription associated with S phase”
EBV and Tumorigenesis
“Transformed B-cells always contain extrachromosomal EB virus genomes”–integration of viral genome is requires.
Burkitt’s syndrome: “translocation places the c-myc proto-oncogene on chromosome 8 under transcriptional control of an immunoglobin gene”
“Malaria is a cofactor because it inhibits cell-mediated immunity in children.”
“EB virus also infects epithelial cells, and is highly associated with nasopharyngeal carcinoma.”
HHV8 and tumorigenesis
“AIDS-associated Kaposi’s sarcoma (KS) is the most frequent neoplasm occurring in persons with AIDS. 15 - 20% of AIDS patient develop it.”
“multiple, pigmented, highly vascularized nodules of the skin”
Viral oncogenes like GPCR “induces VEGF expression and angiogenesis” and cyclin-homolog and LANA antigen.
Structure of retrovirus
“enveloped viruses with a nucleocapsid containing two identical copies of positive sense, single-stranded RNA about 10 kilobases long”
Replication of retrovirus
“virion RNA is copied into double-stranded DNA by a viral protein called reverse transcriptase”
“the very 5’ and 3’ ends which become duplicated during reverse transcription, and are called Long Terminal Repeats (LTR”
“The initial product is a DNA-RNA hybrid. A ribonuclease specific for DNA-RNA hybrids (RNase H, another activity of reverse transcriptase) degrades the viral RNA.”–do the 2nd
“viral protein integrase catalyses this process. The LTRs are important in integration. Once integrated, it is called a provirus.”
“Synthesized mRNA is either made into proteins or packaged with it to virions”
Acute transforming virus (retrovirus) and tumorigenesis
“The acute transforming virus, Rous sarcoma virus (RSV), induces sarcoma rapidly in chickens”
“RSV and carries a viral oncogene, called src .”
“src gene encodes a tyrosine specific protein kinase that has 50-100 times higher affinity”
“Defective, acute transforming retroviruses can not produce infectious virions unless the cell is also infected with a related nondefective retrovirus,”
Because gag, env, pol segments are replaced with oncogenes.
Non-acute transforming virus (retrovirus) and tumorigenesis
“the provirus is often found integrated adjacent to a proto-oncogene. This is a rare event and often takes years.”
“places the proto-oncogene under the control of the highly active retroviral promoter”
Need not helper virus, because by itself its not defective.
Oncogenic retrovirus in human
“The only oncogenic human retroviruses are human T-cell leukemia virus-1 and 2 (HTLV-1,2).”
“the etiologic agent of adult T-cell leukemia (ATL).”
usually asymptomatic
“following a long latency of 10 - 30 years”
“Viral tax protein is a transcription factor and induces IL-2 and it’s receptor and may set up an autocrine loop, predisposing to transformation.”
Hep B/C virus and tumorigenesis
“Hepatitis B virus causes primary hepatocellular carcinoma the leading cause of cancer deaths worldwide”
“Tumors have integrated of hepatitis B virus DNA. Mechanism of tumor induction is unclear and likely very complex.”
Hep C is RNA, flavivirus isnt made part of host genome
For both, constant degradation and regeneration of hepatocytes via immune responses lead to cell transformation.
For Hep B, Reverse transcriptase is used like retrovirus (very early), but in a different timeline (very late).
