Patrick Moore (University of Pittsburgh, USA)
“Why Do Viruses Cause Cancer?”
• Cancer endangers virus as well as host
• Viruses non-transmissible in tumors (eg latency, pseudo-latency)
• Virus populations
Limited resource hypothesis: enhancing lyric virus replication
tumor virus targets at G1 phase
Infection is responsible for ~1 in 5 human cancer cases
The KS epidemic (SEER data) 1975-2014
– RDA-based discoverer of KSHV 1994 Science
– Genome of KSHV Nat Rev Cancer 10: p707 (2010)
– KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway
Oncogene 1997 15, Gao SJ teal
• interferon inhibition cell transformation
• Anti-oncogenes and oncogenic proteins of IRF 1 and 2 (1993)
• Takaoka et al Nature 424,:516 (2003). Survival of p53-null and wild-type mice after VSV infection
•
Innate immunity like gene vs tumor suppressor genes
Innate immunity signaling pathways might have taken over (become) tumor suppressor genes to
KSHV oncogene comes latency genes (right terminal) vFLIP, vCycline
KSHV innate immune evasion genes (or oncogenes?)
Features of innate immunity
– inhaibit cell cycle
Merkel Cell polyomavirus (MCV)
Digital Transcriptome subtraction (DTS)
Common 9>60%), life-long skin infection
MCV, mutation s to viral flora can cause cancer
Mutations tumor-specific truncated T antigen
Molecular steps in MCV carcinogenesis
Kate wins let explaining Rp in contagion (2011) disease transmission: epidemiology
Latent-lytic replication regulated by transcription
Keanu et al Cell host and microbes (2013) and PNAS (2017). Fbw7/Skp2 (ubiquitin ligand)
SCF E3 ligament regulate MCV LT stability
SCF E3 inhibition activates MCV transmission
MCV VP1 antibody neutralizes
MCV protein-mediated viral latency
MCV: mechanisms to repress viral replication