Harald zur Hausen (German Cancer Research Center, Germany)
“Discovery and Early Studies of EBV in Burkitt’s Lymphoma and NPC”
- EBV provides a step in the malignization of pre-malignant NPC lesion (methylation of p16)
- Endemic multiple sclerosis
- TGFb is an inducing agent for EBV lytic replication
- Vit D deficiency -> TGFb increase -> EBV reactivation
- EBV enhances TT virus replication
- In dually infected BL or LCL cells, EBV and BMV bovine milk factor –> low sun exposure/Vit D deficiency –> TGFb increases –> EBV reactivation –> inflammation → tissue destruction –> multiple sclerosis
From Ming-Han
- In Henle’s lab before and identify EBV is specific to IM and BL (JV 1967; 1: 1174-85) and Identify abnormal ch 12. Whether EBV cause chromosome instability?
- Prove EBV associated to BL and NPC (ISH)
- NPC: epidemiological factors of NPC?
- p16 inactivation (Tsang et al) and Cyclin D1 activation (Tsang et al, PNAS 2012).
- Hypothesis: whether EBV cause NPC for the prp-malignant NP cells???
- BL: cMyc translocation is important (RAG1/2; NEHJ)
- Current research: Streker and de villiers: TT-like particles (23: 11-2006)
- Whether EBV stimulate TT virus replication? For example: CMV, Herpesvirus, adenovirus infected cells can cause lytic replication in the non-permissing cells.
- 概念：人類的病毒在人類不會lytic但是人類病毒在動物細胞可以。反之亦然。是否動物的病毒感染人類造成chronic infection而導致MS?
- ＠發現：HSV infected HL secrete small viral particles? (Lacent 2001, 257: 381-384).
- @May animal viruses DO NOT replicate in Human but do lytic cycle in animals can cause human diseases? On the other hand, is that possible that human virus cause tumor in animals?
Model: He used milk cow viruses (episomal type; DNA virus) to test his hypothesis
- These viruses can infect human cells (RNA, protein, replication).
- Correlation: children drink milk is associating to the deficiency of VitD later, Reactivation of latent HSV infection (EBV, HHV6, VZV also), and also the high MS factor. On the other hand, if children drink mother milk>6 month and live in tropical regions may have fish factor. Importantly, the reduced of VitD is associating to the elevated MS factor.
- Why VitD and MS?
- elevated VitD3 receptor is associating to lower TGFB secretion
- TGFB elevate EBV lytic cycle.
- Whether low vitD-> big TGFB-> high EBV activation?
Result:
- EBV infection can elevate cellular small DNA virus activation!! whether these small viral particle causes chronic inflammation?
- Model: many cells infected by milk virus and many cell infected by EBV: few cells with both. these cells stimulate viral reactivation.
Q: what EBV protein cause these milk viruses from cows super replication? UNKNOWN!!!
Q: Whether these small viruses alter human immune responses? UNKNOWN and ongoing.
Q: by Rickonson: connection between infection and cancer?
A: HPV and smoker and lung cancer: actually people found 20-50% lung cancer actually not smoker.
A: Vaccine against virus: like VSV and rebulla and HPV: nearly 100% protective.
Q: EBV vaccine and NPC?
A: problem: since EBV mostly do replication in oral epithelial cells, that means the vaccine need to produce high level of AB in Saliva…