![Page 1: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/1.jpg)
Tumor viruses of animals
Ab Osterhaus
Department of Virology
• veterinary importance?
• lessons for human cancer?
• zoonotic potential?
![Page 2: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/2.jpg)
History of tumor virology (1/2) Javier et al, RT Cancer Res. 2008
![Page 3: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/3.jpg)
History of tumor virology (1/2) Javier et al, RT Cancer Res. 2008
Ciuffo
Ellerman and Bang
![Page 4: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/4.jpg)
Peyton Rous: discovered avian virus
that induced tumors in chickens(1911)
Photo:The Rockefeller University Archives. Javier et al, RT Cancer Res. 2008
![Page 5: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/5.jpg)
History of tumor virology (1/2) Javier et al, RT Cancer Res. 2008
Bittner
Shope
Gross
![Page 6: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/6.jpg)
Animal tumor viruses as models
Javier et al, RT Cancer Res. 2008
![Page 7: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/7.jpg)
Molecular epidemiology of
gibbon hepatitis B virus transmissionSuwanna Noppornpanth et al 2003
Fig. 1. Phylogram based on nucleotide
sequences of the complete S gene using the
Kimura two-parameter matrix and neighbour-
joining method. Bootstrap values (1000 total)
of 70 % are indicated on the branches.
Human and nonhuman primate HBV were
compared to gibbon and human HBV
isolates identified in this study.
![Page 8: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/8.jpg)
Animal tumor viruses:
of veterinary importance (Truyen and Loechelt, 2006)
![Page 9: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/9.jpg)
![Page 10: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/10.jpg)
MMTV vs HMTV
MMTV causes breast cancer in mice (Bittner, 1936)
HMTV / Pogo virus associated with human breast cancer?
~ 660-bp env sequence similar to MMTV in breast cancers
~ env and LTR HMTV insertions in chromosomes (~MMTV)
~ HMTV in primary breast cancer cells
~ …
![Page 11: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/11.jpg)
Retroviruses and tumors: poultry
Avian leukosis/sarcoma (L/S) group caused by α-retroviruses
tumor related mortality (acute or slow)
reduction egg production
subclinical immunosuppression
Endogenous versus exogenous ALVs
Acute transforming ALVs carry viral oncogenes
Slowly transforming ALVs insert LTR: activation of cellular oncogens
![Page 12: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/12.jpg)
Retroviruses and tumors:
sheep and goats
Jaagsiekte caused by a β-retrovirus:
transmissible ovine pulmonary adenocarcinoma
tumor induction by respiratory tropic JSRVs Env protein
transformation upon binding hyaluronidase-2 receptor
aerosol transmission to suckling lambs
incubation time about 9 months
lung neoplasia (type 2 pneumocytes:
ovine pulmonary adenocarcinoma)
full blown disease after 1-3 years
enJSRVs Env supposed to play a key role in placentation
![Page 13: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/13.jpg)
Involvement of enJSRV Env and Hyal-2 in placentationVarela et al, Ann N Y Acad Sci. 2009
mononuclear trophoblast cell
giant binuclear cell
endometrial luminal cell
cotyledone formation
![Page 14: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/14.jpg)
Varela et al, Ann N Y Acad Sci. 2009
![Page 15: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/15.jpg)
Retroviruses and tumors: cats
Feline leukemia virus: a γ-retrovirus
worldwide distribution (1-10%)
disease manifestations:
lymphosarcoma, “AIDS” / anaemia …
replication-defective viruses (feline
sarcoma viruses) carrying oncogenes
harbour oncogenic potential
horizontal and vertical transmission
natural and vaccine induced immunity
elimination and vaccination strategies
successful
![Page 16: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/16.jpg)
![Page 17: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/17.jpg)
Primate and feline lentiviruses
Yamamoto et al, Cell Science 2006
![Page 18: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/18.jpg)
Retroviruses and tumors: cattle
Bovine leukosis virus: a δ-retrovirus
worldwide distribution (up to 100%)
transmission by infected lymphocytes (and vertical)
30% develop lymphocytosis and 5% tumors
persistent lymphocytosis: increased cell proliferation
eradication by screening programs
![Page 19: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/19.jpg)
Phylogenetic analysis of 519 bp of LTR region sequenced from 81 strains of HTLV-I/STLV-I
Slattery J P et al. Genome Res. 1999;9:525-540
©1999 by Cold Spring Harbor Laboratory Press
![Page 20: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/20.jpg)
Polyomaviruses in animals and humans
Mouse polyoma virus: tumors in susceptible mouse strains
SV40: rhesus monkeys
persistent infection in kidneys
` polio vaccination associated tumors
(rhesus versus cynomolgous kidneys)?
Human BKV: persistent infection in kidneys
nephropathy (immune-compromised)
tumors in experimentally infected mice
prostate cancer?
Human JCV: progressive multifocal leukoencephalopathy
(PML: in the immune- compromised)
tumors in experimentally infected mice
Human KI and WU viruses???
![Page 21: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/21.jpg)
Mammalian papillomaviruses: Cattle
Six BPV types:
BPV 1 cutaneous fibropapilloma
BPV 2 cutaneous fibropapilloma
BPV 3 cutaneous fibropapilloma
BPV 4 intestinal tract papilloma
BPV 5 teat fibropailloma
BPV 6 teat papilloma
Bracken fern major co-factor for invasive
carcinomas alimentary tract (BPV 4) and
bladder (BPV 2)
BPV 1and 2 also in horses
M.S. Campo / Virus Research 89 (2002)
![Page 22: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/22.jpg)
Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids.
Nasir L, Campo MS. Vet Dermatol. 2008 Oct;19(5):243-54.
![Page 23: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/23.jpg)
Bovine papillomavirus (BPV-4) lesions in the alimentary tractM.S. Campo / Virus Research 89 (2002)
![Page 24: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/24.jpg)
M.S. Campo / Virus Research 89 (2002)
![Page 25: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/25.jpg)
M.S. Campo / Virus Research 89 (2002)
![Page 26: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/26.jpg)
Animal papillomaviruses: Horses
EPV causes benign warts
BPV 1 and 2 cause equine sarcoid
invasive fibrosarcoma-like processes
no metastasis
constant expression of E5
M.S. Campo / Virus Research 89 (2002)
![Page 27: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/27.jpg)
Papillomaviruses: dogs
COPV 1 and 2: benign warts (skin, mouth, genital, conjunctiva)
More than 25% of dogs may be affected in kennels
Experimental vaccines work (whole virus, VLP, L1, E1, E2 and E7)
probably on the basis of a specific T cell reponse
M.S. Campo / Virus Research 89 (2002)
![Page 28: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/28.jpg)
Herpesvirus evolutionary tree
Fish & Amphibian Mammalian & Avian Invertebrate
![Page 29: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/29.jpg)
Herpesviruses’ Success:
Co-evolution of Virus and Host
![Page 30: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/30.jpg)
Marek’s Disease: Gallid herpesvirus 2K.W.Jaronski et al.,Exp. Rev. Vaccines 2006
•alpha herpesvirus
•increasingly virulent strains last decades
•in face of comprehensive vaccination
•neurological symptoms
•chronic wasting
•multiple lymphomas:
•solid tumors in viscera and musculature
•MD-induced oncogenesis: many GHV-2 genes
![Page 31: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/31.jpg)
Gallid Herpesvirus 2: Oncogenesis
K.W.Jaronski et al.,Exp. Rev. Vaccines 2006
![Page 32: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/32.jpg)
![Page 33: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/33.jpg)
![Page 34: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/34.jpg)
Retroperitoneal Fibromatosis Herpesvirus Pathology
Retroperitoneal fibroma Bundels and fascicles, no vessels
Anti HHV8 LANA MoAb
Russel et al The Vet.J.,2009
![Page 35: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/35.jpg)
![Page 36: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/36.jpg)
Rhesus Rhadinovirus Pathology
Lymphocyte hyperplasia Vascular hyperplasia Follicular hyperplasia
Follicular dissolution Proliferative and hyalinized vessels
(~multicentric Castleman disease)
Russel et al The Vet.J.,2009
![Page 37: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/37.jpg)
Malignant Catarrhal Fever: Ovine Herpesvirus 2
inapparent infection in natural host!
accumulation of CD8+ T cells in organs of other ungulates
![Page 38: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/38.jpg)
CLOSE
Seal gammaherpesvirus
in immunocompromised mice Martina et al 2007
Myoepitheliomas (arrow head) in salivary gland
of a mouse treated with cyclosporin A and
infected with phocid herpesvirus type 2
The neoplasm consists of interlacing bundles of
spindle cells with marked anisokaryosis and
a variable number of mitoses (arrowhead).
![Page 39: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/39.jpg)
Seal gammaherpesvirus
in immunocompromised African green monkeys Martina et al 2007
Follicular hyperplasia in the spleen of an African green monkey
treated with cyclosporin A and infected with phocid herpesvirus
type 2
The germinal centres (arrowheads) are markedly expanded and
retain a peripheral mantle zone.
Germinal centre, showing numerous mitoses (arrowheads) and
variation in cell type.
![Page 40: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/40.jpg)
CONCLUSIONS
Importance of animal tumor viruses:
Veterinary: original pathogens for animals
~ wildlife
~ husbandry
~ companion animals
Animal models: studies of pathogenesis
and intervention strategies
Zoonoses: human or public health, heterologous species?
(examples in Herpes-, Papova-, and Retroviridae)
![Page 41: veterinary importance? lessons for human cancer? zoonotic ... · Retroviruses and tumors: sheep and goats Jaagsiekte caused by a -retrovirus: transmissible ovine pulmonary adenocarcinoma](https://reader036.vdocuments.mx/reader036/viewer/2022062605/5fd7e44a0d037d637079470e/html5/thumbnails/41.jpg)
Emerging
virus infections
Department of Virology