Retroviruses

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Retroviruses

• (1) Oncoviruses
• Alpha retrovirus- avian C type viruses (RSV)
• Beta retrovirus- B and D type (MMTV, Mason-Pfizer
• Gamma retrovirus- mammalian C type viruses (MLV)
• Delta retrovirus- HTLV-1
• Epsilon retrovirus- walleye dermal sarcoma (WDSV)

(2) Lentiviruses-induce a slow, wasting disease
(HIV-1, HIV-2, SIV EIAV
(3) Spumaviruses-foamy viruses, induce persistent
infection without
clear pathology
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Retroviral Receptors
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Schematic representation of the three different
states of the retroviral env protein during viral
entry
Tripet, B. et al. J. Biol. Chem.
200427920836-20849
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Interference
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Retroviral Promoters
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Pseudotypes
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Retroviral Transformation

• Acute transforming/transducing retroviruses
• Induce tumours of a polyclonal origin
  within weeks
• to months after administration.

(2) Non-transducing retroviruses Induce tumours
of a monoclonal origin within months
to years after inoculation
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There are many pathways affected by oncogenes and
tumor suppressor proteins
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Proto-oncogenes encode components of growth
factor signal transduction pathways
Components shown in yellow are known
proto-oncogenes
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Four classes of oncogenes

• Class One oncogenes that mimic growth factors to
  induce cell proliferation
• Rare only two have been identified
• Sis
• from simian sarcoma virus a secreted protein
  that mimics PDGF
• from PI-FeSV a cat sarcoma virus

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Class Two Mutated Receptors

• Oncogenes that result from mutations of
  cell-surface receptors, usually resulting in an
  overactive or constitutive protein-tyrosine
  kinase (PTK).
• Examples
• fms from McDonough feline sarcoma virus
  CSF-1 receptor
• kit from HZ4 feline sarcoma virus SCL
  receptor
• erbB from avian erythroblastosis virus
  epidermal growth factor (EGF) receptor
• ros UR2 avian sarcoma virus related to
  insulin receptor
• sea S13 avian sarcoma virus related to human
  growth factor (HGF) receptor

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Class Three Intracellular transducers

• 4 types of oncogene transducers
• Protein-tyrosine kinases
• add a phosphate to specific tyrosine amino acids
• Protein-serine/threonine kinases
• add a phosphate to specific serine or threonine
  amino acids
• G-protein (Ras) proteins
• Trimeric GTPases that bind GTP to become active
  as signal transducers
• Phospholipase C (PKC)
• Activated by certain G-proteins to trigger
  inositol phospholipid signaling pathway

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Class Four transcription factor oncogenes

• Examples
• Jun
• Fos
• Myc (many examples in chicken, cat leukosis
  viruses)
• Myb (chicken myeloblastosis virus)
• Rel (NF-kB family - turkey reticuloendotheliosis
  virus)
• Maf (interact with Fos and Jun chicken sarcoma)
• erbA (thyroid hormone receptor from chicken
  erythroblastosis virus)

Transcription factor AP1
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