Viruses and cancer Flashcards
Give examples of retroviruses
avian leukosis
Feline retroviruses
Jaagsiekte sheep retrovirus
bovine leukosis
What cancers do avian leukosis cause?
lymphoid, myeloid tumours, sarcomas
What cancers does feline retrovirus cause?
lymphoid tumours
What cancer does Jaagsiekte sheep retrovirus cause?
lung adenocarcinoma
What cancer does bovine leukosis cause?
lymphoma
What type of virus is an RNA virus?
retrovirus
What type of viruses are DNA viruses?
Herpesviruses e.g., marek’s disease virus
Papillomaviruses
What cancer does Marek’s disease virus cause?
lymphoid tumours
What is a proto-oncogene?
a normal gene that plays a role in regulating cell growth, differentiation, and division
can become an oncogene, leading to uncontrolled cell proliferation and potentially cancer
Give examples of protein coded by proto-oncogenes
receptor kinases
adaptor proteins
small binding proteins
kinases
transcription factors
What cause proto-oncogenes to become oncogenes?
Mutations in cellular proto-oncogenes:
- viral transduction - can result in overproduction of protein homologous to cellular oncogene
- viral insertion - can affect the production of a functional cellular oncogene
What are the structural components of a simple retrovirus?
What are the main mechanisms of retroviruses causing cancer?
Transduction of an oncogene
Insertional Activation
Other mechanisms e.g. via specific viral proteins
Describe retroviral transduction
The virus carries its own cellular oncogene which is inserted into the host genome
The oncogene is switched on and causes rapid cell proliferation
How is rous sarcoma virus different to other retroviruses?
In most cases acquiring a cellular oncogene results in loss of essential retroviral genes – therefore virus is “defective” and requires “help” in order to replicate
These “defective” viruses do not spread between hosts and usually arise de novo (anew) in each infection
RSV contains v-src – homologous to c-src but with C terminal deletion that renders it constitutively active (always on) => uncontrolled cell division and cancer
Describe insertional activation
Retrovirus infects a host cell and integrates its DNA into the host genome.
If the viral DNA inserts near a proto-oncogene, its long terminal repeat (LTR) acts as a strong promoter, increasing oncogene expression.
The excessive expression of the oncogene causes uncontrolled cell growth and tumour formation
Oncogenesis is slower than retroviral transduction
Describe the cellular changes due to rous sarcoma virus
Loss of contact inhibition
Increased cell density
Increased growth rate
Anchorage-independent growth
Tumorigenic in appropriate hosts
Describe the process of avian leukosis virus causing cancer
Transmitted from hen to the egg
Persistent virus infection of hatched chicks
Immunotolerant to viral antigens and develop tumours
ALV subgroups A and B => B lymphocyte tumours
ALV subgroup J => myeloid tumours
Describe the control of avian leukosis
Select virus-free hens by screening eggs before hatching
Check eggs over 14-day period for ALV antigen in albumen by ELISA
Hatch chicks and rear in isolation
Test for ALV antigen in blood
Maintain virus-free breeders, eradicate infected
Virus is susceptible to disinfectants but can be transmitted by mating
Explain the mechanism bovine leukaemia virus causes cancer
Causes enzootic bovine leukosis
Virus infects B lymphocytes and becomes latent
No free virus in blood
Antiviral antibodies in persistently infected cattle
The viral Tax protein transactivates cellular genes
Products of transactivated cellular genes may be oncogenic => lymphocytosis, lymphoma
Describe the mechanism of Jaagsiekte sheep retrovirus causing cancer
JSRV replicates only in type II pneumocytes and Clara cells
Replication leads to transformation of every cell
Viral Env protein switches on signals for cell division – activates cellular signalling pathways
Causes ovine pulmonary adenocarcinoma (OPA)
What are the clinical signs of Jaasiekte sheep retrovirus?
Loss of condition
Dyspnoea
Clear or frothy fluid from lungs can appear as discharge dripping or pouring from the nose
Slowly progressive, can die suddenly
How is Jaagsiekte sheep retrovirus controlled?
Respiratory secretions are infectious
Requires close contact
More common in housed sheep
Can eliminate the disease by isolation and culling of diseased animals
Diagnosis by histopathology/RT-PCR
Maintain a closed virus-free flock
What co-factors can be involved in carcinogenesis in cattle?
Bracken - contains a number of immunosuppressive and mutagenic chemicals
Pappilomaviruses:
BPV-2: bladder carcinomas
(enzootic haematuria)
BPV-4: alimentary carcinomas
(oesophageal, rumen, reticulum)
How does Marek’s Disease virus cause cancer?
Virus infection causes transformation of T lymphocytes which form tumours
What are the consequences of Marek’s Disease Virus?
Fowl paralysis
Tumours
Ocular changes
Rapid death in young unvaccinated birds
Immunosuppression
Cutaneous nodules
Describe the interaction of herpesvirus in chickens with host cells
Cytopathic (lytic) and cell-associated
- B-cells, macrophages
Non-productive (latent) and cell-associated
- tumour cells in T lymphocytes
Cell-free and productive
- Feather follicle cells – source of new infectious virus
Describe the pathogenesis of Marek’s Disease virus
Enveloped virus shed from feather follicle cells
Inspired into resp tract
Infected bursa, thymus, spleen
Affect B cells and macrophages => cell death
Affects T cells => cell activation and transformation => tumour
Describe the epidemiology of Marek’s Disease Virus
Carrier status (latency)
Environmental survival (months)
Viral factors (virulence)
Host factors:
- MHC – immune response
- T lymphocyte “ease of transformation”
- Stress
How is Marek’s Disease Virus diagnosed?
Clinical signs + pathology:
- virus isolation
- PCR
- antibody detection
Virus presence alone does not confirm diagnosis in absence of clinical signs
How is Marek’s Disease Virus Controlled?
Disinfection
biosecurity
all in - all out management
vaccination
When are chickens vaccinated against Marek’s Disease Virus?
in-ovo or to day old chicks
