1. Oncolytic Virotherapy
Reovirus: A Prototypical Wild-type Oncolytic Virus
By: Stephen Mayper

2. Cancer Abnormal cell growth
Accumulated genetic & epigenetic alterations
Healthy cells gone “haywire”
Numerous means of immune response evasion

3. Conventional Treatments
Surgery
Tumor removal
Is ineffective against and can induce metastasis
Inherent risk!

4. Conventional Treatments
Radiotherapy
Uses radiation to kill tumor cells
Effective at reducing…
…Tumors!
…Aaaaand healthy cells
Can carry severe side effects
(Creative representation if innocent bystander cell death…)

5. Conventional Treatments
Chemotherapy
Use of pharmaceuticals to kill tumor cells
It works!
…But it kills lots of other cells indiscriminately

6. Emerging Treatment: Virotherapy
Uses an oncolytic virus (OV) to lyse cancer cells
Advantages:
High specificity means fewer side effects
Self-regulating dosage
Lack of contraindications

7. Viruses currently being explored
SV40 virus
Seneca Valley virus
Adenovirus
Parvo virus
Myxoma virus
Mumps virus
Influenza virus
Human Herpes virus
Pseudorabies virus
Vaccinia virus
Coxsackie A virus

8. How does it work? …Get it? Virus can be… Naturally occurring
(It’s a virus in “nature!”)
Virus can be…
Naturally occurring
Genetically engineered
Transcription targeting
Attenuation
Specificity generally determined by antiviral pathway deregulation

9. Example: Adenovirus Therapy Targeting Gliomas
Source: Maruniak, Jim. "Adenovirus." MCB 5505, Honors Virology. University of Florida, Gainesville, FL. 19 Feb Lecture.

10. Another Mechanism of Tumor Cell OV Susceptibility
Source: Chiocca EA. Oncolytic viruses. Nat Rev Cancer Dec;2(12):

11. Reovirus

12. Reovirus Background REOvirus = “Respiratory Enteric Orphan Virus”
Infect human respiratory & gastrointestinal tracts
“Orphaned” because originally not thought to be associated with any disease
Several disease associations discovered since
Reoviruses are pervasive

13. Reovirus Taxonomy Mostly Asymptomatic African Horse Sickness
Family: Reoviridae
Genera Infecting Vertebrates (6)
Orthoreovirus
Orbivirus
Coltivirus
Rotavirus
Aquareovirus
Seadornavirus
African Horse Sickness
Colorado Tick Fever
Blue Tongue Disease
Mostly Asymptomatic
(Percentage of gastroenteritis deaths)
Source: Cann, Alan. "Reoviruses." MicrobiologyBytes. 11 Sept Web. <

14. Reovirus Structure Spherical, 80 nm diameter Non-enveloped
Isometric capsid
Concentric inner and outer capsids
Sometimes middle capsid
(Inner capsid = “core”)
4 core proteins
λ-1, λ-3, μ-2, σ-2
Heat-stable
pH= 3 – 9
Denatured by ethanol

15. Reovirus Genome RNA Double- Stranded Linear
10-12 segments (species- dependent)
Reassortment common in vitro
Encodes viral replication machinery
Source:

16. Reovirus Reproduction
Replicates in the cytoplasm
Encodes its own replication machinery
Antiviral susceptibility
Does NOT fully uncoat
Core is resistant to protease digestion
No uncoating
No destruction by host cell
Genomic RNA stays in the core
Assembled virions form cytoplasmic inclusion bodies
Released via cell lysis
6 – 7 hour replication time

17. Reovirus Replication Illustrated

18. Questions? Comments?

19. Sources
Cann, Alan. "Reoviruses." MicrobiologyBytes. 11 Sept Web. <
Chiocca EA. Oncolytic viruses. Nat Rev Cancer Dec;2(12):
Hammill AM, Conner J, Cripe TP. Oncolytic virotherapy reaches adolescence. Pediatr Blood Cancer Dec 15;55(7): doi: /pbc Epub 2010 Aug 23.
Maruniak, Jim. "Adenovirus." MCB 5505, Honors Virology. University of Florida, Gainesville, FL. 19 Feb Lecture.
Mertens P. The dsRNA viruses. Virus Res Apr;101(1):3-13.
Nettelbeck DM. Cellular genetic tools to control oncolytic adenoviruses for virotherapy of cancer. J Mol Med Apr;86(4): Epub 2007 Dec 19.
Siegel, Robert. "Reoviruses." Stanford University. 1 Feb Web. 20 Apr <
Vähä-Koskela MJ, Heikkilä JE, Hinkkanen AE. Oncolytic viruses in cancer therapy. Cancer Lett Sep 8;254(2): Epub 2007 Mar 23.