Viruses & neoplasia

Question 1

What are examples of retroviruses (RNA viruses) that cause cancer?

Answer 1

Avian leukosis virus – lymphoid, myeloid tumors, sarcomas

Feline retroviruses – lymphoid tumors

Jaagsiekte sheep retrovirus (JSRV) – lung adenocarcinoma

Bovine leukosis virus (BLV) – lymphoma

Question 2

What are examples of DNA viruses that cause tumours?

Answer 2

Marek’s disease virus (herpesvirus) – lymphoid tumours

Papillomaviruses – cause skin & mucosal warts & papillomas in cattle, horses & dogs

Question 3

What is a proto-oncogene?

Answer 3

Normal gene that can become oncogene due to mutation or increased (uncontrolled) expression

Question 4

What are examples of proto-oncogene functions?

Answer 4

Receptor kinases
Adaptor proteins
Small binding proteins
Kinases
Transcription factors

Question 5

How do proto-oncogenes become oncogenes?

Answer 5

Proto-oncogenes are normal genes involved in cell growth. They become oncogenes when overactivated by:
- Mutation (→ c-onc)
- Viral gene insertion (→ affects expression)
- Viral transduction of oncogenes (→ v-onc)

Question 6

What are the main mechanisms by which retroviruses cause cancer?

Answer 6

Transduction of an oncogene
Insertional activation of a cellular oncogene
Other mechanisms via specific viral proteins

Question 7

How does retroviral transduction lead to cancer?

Answer 7

Retrovirus carries viral oncogene & inserts it into host genome

This oncogene is overexpressed, leading to uncontrolled cell growth

Question 8

How does a retrovirus integrate into the host genome?

Answer 8

1. Virus enters host cell via receptor
2. RNA genome is reverse transcribed into cDNA
3. cDNA enters nucleus & is integrated into host genome using viral enzyme integrase
4. Once integrated, viral genome remains in host for life, unless cell dies

Question 9

Why can’t most oncogenic retroviruses be transmitted between hosts?

Answer 9

Acquiring a host oncogene often deletes essential viral genes

Virus becomes replication-defective

Requires co-infection with a helper virus to replicate

Arises de novo in each infection, so not passed between hosts

Question 10

How is Rous Sarcoma Virus (RSV) different from other oncogenic retroviruses?

Answer 10

RSV can still replicate & transmit despite carrying oncogene, unlike most defective oncogenic retroviruses

Question 11

What oncogene does RSV contain, and how does it cause cancer?

Answer 11

RSV carries v-src (viral homolog of c-src with C-terminal deletion) making it constitutively active & leading to uncontrolled cell growth

Question 12

How does Rous Sarcoma Virus (RSV) cause rapid oncogenic transformation?

Answer 12

RSV carries v-src oncogene, which promotes uncontrolled cell division, leading to rapid transformation of normal cells into cancerous ones

Question 13

What are key cellular changes after RSV infection?

Answer 13

Loss of contact inhibition (cells no longer stop growing when they touch each other)

Increased cell density (cells pile up abnormally)

Increased growth rate

Anchorage-independent growth (cells grow without needing a solid surface)

Tumorigenicity (cells can form tumours in appropriate hosts)

Question 14

What type of retrovirus is RSV classified as?

Answer 14

Acute transforming retrovirus, meaning it induces cancer quickly due to direct oncogene activation

Question 15

What is insertional activation in retroviral oncogenesis?

Answer 15

Retrovirus integrates near proto-oncogene (c-onc), leading to its abnormal activation & potential cancer formation

Process of oncogenesis is slower compared to acute transforming retroviruses

Question 16

How do retroviruses cause cancer through insertional activation?

Answer 16

Unlike transducing retroviruses, these retroviruses don’t carry oncogene

Instead, their Long Terminal Repeat (LTR) regions act as promoters & enhancers, increasing transcription of nearby proto-oncogenes

Question 17

What are the two main ways retroviral insertion can activate a proto-oncogene?

Answer 17

Promoter activation – viral LTR promoter enhances transcription of proto-oncogene

Enhancer activation – viral LTR enhancer elements increase expression even if insertion is some distance away

Question 18

What are examples of insertional activation retroviruses?

Answer 18

Feline leukemia virus (FeLV) & Avian Leukosis virus

Question 19

How is avian leukosis virus transmitted?

Answer 19

From the hen to the egg

Chicks hatch with persistent infection & become immunotolerant to viral antigens & develop tumours

Incubation period for tumour development is > 4 months

Question 20

What type of tumors does Avian Leukosis Virus (ALV) cause?

Answer 20

ALV primarily causes B-cell tumours, including:
- Tumours in bursal follicles (due to viral integration activating proto-oncogenes)
- Diffuse liver tumors (resulting from viral recombination & gene capture)

Question 21

How is ALV controlled?

Answer 21

Control by eradication in breeder flocks

1. Select virus-free hens by screening eggs before hatching
2. Check eggs over 14-day period for ALV antigen in albumen by ELISA
3. Hatch chicks and rear in isolation
4. Test for ALV antigen in blood
5. Maintain virus-free breeders

Virus is susceptible to disinfectants but can be transmitted by mating

Question 22

What is Bovine Leukemia Virus (BLV), and how does it cause disease?

Answer 22

BLV is delta retrovirus that infects B lymphocytes, leading to enzootic bovine leukosis

Virus becomes latent in host genome, meaning there is no free virus in blood, but infected cattle produce antiviral antibodies

Question 23

What BLV protein drives oncogenesis and how?

Answer 23

Tax protein activates host genes, causing uncontrolled cell growth

These activated genes may be oncogenic, leading to lymphoma

Question 24

How does the Tax protein contribute to cancer development?

Answer 24

Activates cytokine genes (e.g. IL-2) → promotes immune cell proliferation

Upregulates IL-2 receptors → positive feedback loop for continuous growth signals

Disrupts cell cycle control → causes chromosomal instability

Question 25

How is BLV transmitted?

Answer 25

Via infected cells (e.g. milk, blood) Can spread vertically (mother to calf) or horizontally

Question 26

What disease does Jaagsiekte Sheep Retrovirus (JSRV) cause?

Answer 26

Ovine Pulmonary Adenocarcinoma (OPA) ("panting sickness")

Question 27

How does Jaagsiekte Sheep Retrovirus (JSRV) cause cancer?

Answer 27

Viral Env protein activates cellular signaling pathways, leading to uncontrolled cell division in type II pneumocytes & Clara cells

Question 28

What are key respiratory signs of Jaagsiekte Sheep Retrovirus (JSRV) in infected sheep?

Answer 28

Loss of condition Dyspnea (panting, difficulty breathing) Clear or frothy lung fluid discharge Slow progression, sudden death possible

Question 29

How is JSRV transmitted and controlled?

Answer 29

Spread through respiratory secretions & requires close contact More common in housed sheep Controlled through isolation and culling Diagnosis via histopathology and RT-PCR

Question 30

What is a common DNA virus causing tumours in cattle?

Answer 30

Bovine papillomatosis caused by bovine papillomavirus (BPV) Virus is tropic for epithelial and mucous tissues

Question 31

How does bovine papillomavirus (BPV) persist and contribute to cancer development?

Answer 31

BPV establishes persistent infection & remains latent in host cells Over time, expression of early viral genes activates host signaling pathways, leading to abnormal cell growth

Question 32

What factors increase the risk of BPV-associated cancer?

Answer 32

Bracken fern exposure induces immunosuppression & genetic changes, weakening immune response & promoting neoplastic transformation

Question 33

Why is BPV-associated cancer relatively rare?

Answer 33

Neoplastic progression is slow, multistep process, requiring additional factors like immune suppression & long-term viral persistence for tumour formation

Question 34

What viruses are associated with alimentary and bladder cancers in cattle?

Answer 34

BPV-2: Causes bladder carcinomas & enzootic haematuria BPV-4: Leads to alimentary carcinomas in oesophagus, rumen & reticulum

Question 35

What disease does Marek’s Disease Virus (MDV)/Gallid herpesvirus 2 cause?

Answer 35

T-cell lymphomas in poultry

Question 36

How is Marek’s Disease Virus (MDV) transmitted?

Answer 36

MDV is shed from feather follicle cells & spreads through dander & dust, which is inhaled by other birds, infecting respiratory tract

Question 37

After inhalation, where does MDV disseminate in the body?

Answer 37

Virus spreads via blood to immune organs: - Bursa of Fabricius - Thymus - Spleen

Question 38

What are the clinical signs of Marek’s disease?

Answer 38

Neurological signs (paralysis) Tumors in muscles and organs Ocular changes Immunosuppression Cutaneous nodules

Question 39

What are the effects of MDV on different immune cells?

Answer 39

B cells & macrophages → Undergo cell death, leading to immunosuppression T cells → Initially undergo activation & proliferation, then transform into tumour cells, causing lymphomas

Question 40

What are the three types of virus interactions with host cells in Marek's disease?

Answer 40

Differ depending on cell type Cytopathic (lytic) & cell-associated – Virus kills B-cells & macrophages Non-productive (latent) & cell-associated – Virus remains in tumour cells in T lymphocytes Cell-free & productive – Virus spreads from feather follicle cells, key source of infection

Question 41

What factors make Marek’s Disease epidemiology complex?

Answer 41

Carrier status (latency) Environmental survival for months Viral virulence (mild to highly virulent strains) Host factors, including MHC-dependent immune response & stress levels

Question 42

How is Marek’s Disease diagnosed?

Answer 42

Clinical signs & pathology Virus isolation, PCR & antibody detection (supportive but not confirmatory in absence of characteristic clinical signs) Differential diagnosis is avian leukosis (doesn't cause neurological signs)

Question 43

What are the main strategies for controlling Marek’s Disease?

Answer 43

Disinfection, biosecurity & all-in-all-out management Vaccination using: - Turkey herpesvirus (HVT) - Gallid herpesvirus-3 (SB-1 strain) - CVI988/Rispens (attenuated Gallid herpesvirus-2)

Question 44

How is Marek’s Disease vaccination administered, and how long does immunity take to develop?

Answer 44

Given in-ovo (before hatching) or to day-old chicks Immunity takes 7 days to develop

Question 45

What is the function of the gag gene in a retrovirus?

Answer 45

Gag gene encodes structural proteins, including: - Matrix protein - Capsid protein - Nucleoprotein These proteins form virus structure & protect viral RNA

Question 46

What is the function of the pol gene in a retrovirus?

Answer 46

Pol gene encodes key enzymes needed for viral replication, including: - Reverse transcriptase (converts viral RNA into DNA) - Integrase (helps insert viral DNA into the host genome) - Protease (processes viral proteins for assembly)

Question 47

What is the function of the env gene in a retrovirus?

Answer 47

Env gene encodes viral envelope proteins, which help virus attach to & enter host cells

Question 48

What are Long Terminal Repeats (LTRs) and how do they contribute to viral oncogenesis?

Answer 48

LTRs are repeating sequences at both ends of viral genome that contain promoter & enhancer regions, which regulate gene expression LTRs can: - Increase viral gene expression. - Disrupt normal cellular gene regulation when virus integrates into host genome - Activate oncogenes if they insert near proto-oncogene, leading to uncontrolled cell growth

Question 49

What are endogenous retroviruses?

Answer 49

Proviruses integrated into host genome. If they enter germ cells (sperm or eggs), they are inherited by next generation; if in somatic cells, they are lost when animal dies