FeLV and FIV Flashcards
1
Q
What Family and Genus do FeLV and FIV belong to?
A
- Family: retroviridae
- Genus: Gammaretrovirus (FeLV)
- Lentivirus (FIV)
2
Q
What is the Retrovirus cycle?
A
- Retrovirus attaches to cell
- RNA and reverse transcriptase enter cell
- DNA is made from the viral RNA (reverse transcriptase)
- Viral DNA is integrated into the host chromosome
- mRNA
- new virus parts
- assemblage of virus
- Protease to let new virus exit cell
3
Q
What is the structure of Feline Leukemia Virus (FeLV)?
A
- Enveloped
- ss RNA virus (2 identical RNA genomes)
- Forms proviral DNA in host chromosome
4
Q
How stable is FeLV?
A
- Fairly unstable in dry environment - few hours
- Inactivated by commonly used disinfectants
5
Q
How is FeLV transmitted?
A
- Direct contact is the most common form
- Saliva and nasal secretions (bites, mutual grooming)
- Urine, feces - shared litterboxes and food dishes
- Fairly unstable - fomite transmission unlikely
- Infected mother to kittens:
- in utero
- Milk during nursing
6
Q
What is the Pathogenesis of FeLV?
A
- Oral/nasal contact with virus
- Replication in Tonsil and Local lymphoid tissue
- Mononuclear leukocyte-associated viremia
- Replication in systemic lymphoid tissues
- Replication in Bone Marrow Megakaryocytes and Granulopoietic cells and in intestinal crypt epithelium
- Marrow-Origin viremia PMN’s and Platelets (FeLV IF test +)
- infection of mucosal and glandular epithelium
- Leukemogenesis or Aplasia
7
Q
What are the subtypes of FeLV?
A
- Subtype A:
- Only subtype transmitted between cats
- ~50% of FeLV positive cats
- Has LONG incubation period
- Original Transmitted by FeLV
- Subtype B
- ~50% of FeLV positive cats
- Cats with type A & B are more likely to be persistently viremic and develop disease
- Recombination of FeLV A and endogenous FeLV sequences
- Subtype C
- <1%
- Anemia
- Mutation in FeLV A env
- Subtype T
- <1%
- T-cells
- Immunodeficiency
- Acquire T cell tropism by mutations
8
Q
What is a FeLV Regressive Infection?
A
- Virus replication becomes contained by effective anti-viral response by the host
- Undetectable or very low levels of viral replication in blood or tissues - vey low risk of transmission
- Minimal incidence of disease
- Latent infection:
- VIral genome (provirus) is present in bone marrow stem cells (detectable by PCR)
- No infectious virus is actively produced
- Reactivation of infection in some cat
9
Q
What is Progressive infection of FeLV?
A
- characterized by ineffective anti-viral response by the cost - cannot contain virus replication
- Persistent FeLV replication (Viremia):
- Lymphoid tissues, bone marrow, mucosal and glandular epithelium
- Likely to develop diseases & transmit viruses
- Likelihood of progressive infections; natural existence increases with age
- ~100% of kittens 6 weeks old
- ~30% kittens 6 months
- 5015% a>12 months
10
Q
What is the Pathogenesis of FeLV?
A
- Enters lymphoid cells/bone cells
- Degenerative disease) - non-neoplastic disease
- Neoplastic disease
- Lymphoma, Erythroleukemia
- Granulocytic, Erythroleukemia, lymphoblastic leukemia
- Megakaryocytic leukemia
11
Q
compare and contrast the advantages and Disadvantages of Intranasal and Intramuscular inoculation?
A
- Intranasal:
- Stimulates mucosal & systemic immunity
- Less affected by maternal antibodies
- Intramuscular:
- Lymphoma
- Erythro-, Granulocytic, Lymphoblastic, Megamarycyocytic Leukemia
12
Q
What cells does the Degenerative disease of FeLV form?
A
- Lymphoid cells
- Bone Marrow
13
Q
How do Lymphoid cells degenerate during FeLV
A
- Progressive loss of B & T cells and dysfunction of immune cells
- Induces immunosuppression ⇢ secondary infection
- ~50% cats with chronic illnesses (URI, stomatitis, abscess, etc)
- Thymic atrophy in kittens - retarded growth, early death
- Rarely, immune-mediated diseases:
- Immune-complex glomerulonephritis, polyarthritis, Immune-mediated thrombocytopenia, immune-mediated hemolytic anemia (IMHA)
14
Q
What happens to bone marrow with degenerative FeLV?
A
- All bone marrow cell can be infected
- Anemia (mostly non-regenerative) is common
- Thrombocytopenia
- Myeloblastopenia - very low WBC (<3000/ul) diarrhea, anorexia, vomiting - resembles feline panleukopenia infection
15
Q
What are the chances of cats developing lymphoma/leukemia with neoplastic FeLV?
A
- Cats w/FeLV 62x higher chance
- FeLV+ cases in lymphoma/leukemia patients have been declininc from ~80% (‘80s-‘90s) to <20% (late ’90s)
16
Q
What oncogenic mechanisms do viruses utilize?
A
-
Direct (shorter time to induce malignancy)
- virus has viral oncogenic genes (polyomavirus)
- Enhance proto-oncogenes in the host genome (FeLV)
-
Indirect (longer time to induce malignancy) (FIV, HCV)
- Chronic nonspecific inflammation
- Disruption of tumor immune surveillance
17
Q
What is a proto-oncogenes?
A
- Normal cellular genes involved in cellular growth and development
- Can cause uncontrolled cell growth if something goes wrong
18
Q
What is FeLV-induced oncogenesis?
A
- FeLV causes malignancy by randomly inserting FeLV genome near a cellular proto-oncogene
19
Q
What is Feline induced lymphoma?
A
- 4 types based on their most frequent anatomic locations
- Thymic
- Alimentary
- Multicentric
- Atypical/extranodal
20
Q
What is FeLV-induced Thymic (mediastinal) lymphoma?
A
- Cats ~2 yr
- Rapidly progressive
- 80-90% cases positive for FeLV
- Thoracic effusion, dyspnea, coughing and cyanosis
- Primarily T-cell malignancies
21
Q
What is Alimentary lymphoma caused by FeLV?
A
- Most common form - weaker association with FeLV
- 0-30% cases positive for FeLV
- GI tract +/- extraintestinal involvement (surrounding ln, kidneys, liver, etc
- Usually in middle-aged to older cats
- Clinical signs related to renal or intestinal dysfunction:
- weight loss, uremia, intestinal blockage, kidney failure
- Alimentary lymphomas are either B or T-cell phenotypes
22
Q
What is FeLV induced Multicentric lymphoma?
A
- Visceral lymph nodes - most commonly mesenteric
- Liver and spleen can be involved
- Cats of wide age range (young to middle aged)
- Clinical signs related to lymph nodes and organs involved: Enlarged LN, generalized malaise, anorexia, debilitation
- Primary T-cell malignancies
23
Q
What is FeLV induced Atypical/extranodal lymphoma
A
- Solitary tumors in kidneys, CNS, eyes, nasal cavity, heart or skin
24
Q
What are the types of FeLV-induced Leukemia?
A
- Lymphoblastic leukemia
- Myeloid leukemia
25
Q
What is FeLV induced Lymphoblastic Leukemia?
A
- Most common
- Immature, poorly differentiated lymphoblasts infiltrate bone marrow and lymphatic organs (spleen, liver, LN) ⇢ replacing normal hemopoietic cells ⇢ neutropenia, thrombocytopenia and anemia
- Leukocytosis in blood due to increased neoplastic lymphoblasts
- Non-specific clinical signs (anorexia, weakness, vomiting, diarrhea, fever)
26
Q
What is FeLV-induced myeloid leukemia?
A
- Erythroleukemia, Myelomonocytic leukemia, Megakaryocytic leukemia
- Immature, poorly differentiated blastocytes infiltrate bone marrow and lymphatic organs ⇢ replacing normal hemopoietic cells ⇢ cytopenias of one or multiple lineages in blood
- Blastocytes infiltrates lymphatic tissues
- Non-specific clinical signs (anorexia, weakness, vomiting, diarrhea, fever)
27
Q
What is Feline Sarcoma Virus (FSV)?
A
- Arises from rare recombination of FeLV provirus and host proto-oncogenes
- Partial/total loss of provirus gag gene, env gene, and pol genes
- FSV is replication-defective - does NOT naturally transmit to other cats
- Associated with multicentric fibrosarcoma of young cats (<3-5 yr)
- Multiple, ulcerative or nodular, non-healing skin lesions - CAN recur after excision
- Grow rapidly
- Metastasis to internal organs can occur later
- Associated with 2% of fibrosarcoma
- Different from injection site or vaccine-associated fibrosarcoma
28
Q
What is the goal of FeLV diagnosis?
A
Detect progressively infected cats
29
Q
How is FeLV diagnosed?
A
- Detection of virus in plasma, serum or whole blood
- Detection of virus antigen (p27)
- ELISA or Immunochromatographic tests
- Detection of Virus
- IFA
- Virus isolation
- Detection of viral genome
- Viral RNA or proviral DNA by RT-PCR or PCR
- Detection of virus antigen (p27)
30
Q
Can FeLV be diagnosed with the detection of Antibodies?
A
- No, not useful
- false positives from:
- maternal ab
- vaccination
- Ab endogenous FeLV sequences
- Abortive and regressive infections
31
Q
What are the ELISA/immunochromatographic tests for FeLV?
A
- In-clinic screening tests
- For viral antigen (p27) in peripheral blood
- saliva testing less sensitive/reliable
- Most cats become Positive within 1 month after initial exposure
- When seroprevalence is low (1-5%) the majority of positives can be false-positives
- Confirm positive using a different test (IFA, RT-PCR)
32
Q
When should a cat be retested if their initial FeLV test is negative but they had a suspected exposure?
A
1 - 2 months after the last potential exposure
33
Q
What are the different testing strategies for FeLV?
A
- Test all new cats at adoption/entering shelters
- segregate (if possible) with follow-up testing 60 days later
- Test at-risk cats
- sick, cats w/oral diseases, known FeLV exposure, multi-cat households with unknown FeLV status
- Test all cats from households with a history of FeLV
- Test all cats before vaccination
- Blood donor cats should be checked for FeLV antigen and provirus
- Bite wounds are high risk events - test again in 60 days
34
Q
What is the prognosis for cats with FeLV?
A
- One study:
- 85% cats with progressive FeLV infection at the time of dx die w/in 3.5 yr (uninfected cats 5-6 yrs)
- 50% die from immunosuppression
- ~12% from severe non-regenerativeanemia
- 5-10% from cancer
35
Q
How can FeLV be prevented/contolled?
A
- Vaccination, Testing and elimination (from social pools)
- Disinfection - FeLV is fairly unstable in most environment
- Keep FeLV+ cats indoors
- ⇣ transmission
- ⇣ potential exposure to other infectious agents
- Avoid placing progressively infected cats with other cats with compromised immune systems or geriatric cats with chronic disease
- Regular checkup for asymptomatic cats
- Low risk of virus transmission from regressively-infected cats
- look out for reactivation
36
Q
What Vaccines exist for FeLV?
A
- Inactivated FeLV vaccines:
- Nobivac FeLV (Subtype A&B) - whole virus
- Fel-O-Vax (subtypes A & D) - whole virus
- Leukocell 2 - (subtypes A, B, C) - subunit vaccine
- Recombinant FeLV vaccine:
- Furevax recombinant FeLV - env & gag genes of a FeLV subtype A in Canarypox vector
37
Q
What is the recommended vaccination protocol for FeLV?
A
- Recommended for use in all kittens up to and including 1 year of age
- Booster recommended for cats at high exposure risk
- Not recommended for FeLV+ cats and indoor cats with no exposure
- ALWAYS test first - unless FeLV infection is unlikely
- (ie indoor mother cat FeLV-, kittens had NO exposure to other cats)
38
Q
What does the FeLV vaccine do?
A
- Decreases the rate of:
- Transient & persistent viremia
- Latent infection
- Development of FeLV-related diseases
39
Q
What is the structure of Feline Immunodeficiency virus (FIV)?
A
- Enveloped
- ssRNA
- 5 subtypes (A, B, C, D, E, and putative F) based on env gene
- A & b predominant in US
- diverse field strains
40
Q
What is the prevalence of FIV?
A
- ~2.5% in the US
- About 0.3% are co-infeted with FeLV
- 12-14% or mor of all sick cats have FIV
- avg age 5yr
- intact male
41
Q
How is FIV transmitted?
A
- Primarily through biting
- Blood transfer
- mucosal contact
- infected queen to kittens
- through milk
42
Q
What is the stability of FIV?
A
- Fairly unstable in dry environment (few hours)
- fomite transmission not important
- inactivated by commonly used disinfectants
43
Q
What are the cell targets of FIV?
A
- CD4+ T Cells
- Dendritic cells
- macrophages
- CNS cells
44
Q
What is the staging of a FIV?
A
- Acute infection
- asymptomatic carrier (clinical latency)
- AIDS-related Complex
45
Q
What is the acute infection stage of FIV like?
A
- primary viremia
- Transient and mild unspecific signs:
- Fever (2weeks)
- neutropenia (2-4 wks)
- gingivitis
- enteritis
- conjunctivitis
- URI
- depression
- generalized lymphadenopathy (2-9mo)
46
Q
What happens during the latent phase of FIV?
A
- Strong antiviral immunity (humoral & CD8+ T cells) keeps viremia at low levels
- CD4+ T cells progressively decline
- Duration can be dependent on the FIV strain and host factors
47
Q
What happens during the end stage of FIV?
A
- Feline AIDS - chronic, recurrent diseases
- Progressively decreased CD4+ T cells & B cell proliferation ⇢ CD4+ / CD8+ ratios decrease
- High circulating viral load
- Opportunistic infections
48
Q
What diseases are associated with FIV?
A
- Immunodeficiency and opportunistic infections
- Myelosuppression
- Immune-mediated diseases
- Tumors
- Neurological dysfunction
49
Q
Why is Immunodeficiency and opportunistic infections important in cats with FIV?
A
- most clinically important consequence of FIV
- Clinical signs usually reflect secondary diseases
- Usually occurs in later stages of infection
- Due to ⇣ CD4+ T cells and other changes that lead to abnormal function of immune cells
50
Q
What are the frequent secondary infections in cats with FIV?
A
- FeLV
- FHV
- FCV
- FIP
- Demodex
- Cryptococcus
- Candida
- Isospora
- Hemotropic Mycoplasma spp
- Pseudomonas
- Otodectes
- Mycobacteria
- others
51
Q
What are the common illnesses of cats with FIV?
A
- Chronic gingivostomatitis
- Fever
- Skin abscess
- Lymphadenopathy
- URI
- Ear infections
- Weight loss
- diarrhea
- chronic rhinitis
52
Q
Why are immune related diseases are associated with FIV?
A
- ⅓ of FIV+ cats are hypergammaglobulinemic (polyclonal)
- due to chronic inflammation, activation of B cell subsets
- ⇡ immune-complexes
- Immune-mediated hemolytic anemia, immune-mediated glomerulonephritis
53
Q
Why are Tumors associated with FIV?
A
- FIV+ cats are 5x more likely to develop lymphoma or leukemia
- Indirect role of FIV in oncogenesis
- Lymphoma (mostly B cell) is most common in various organs
- Other tumors:
- Squamous cell carcinoma, mast cell tumor, fibrosarcoma
54
Q
Why is neurological disfunction associated with FIV?
A
- ~5% of symptomatic FIV-infected cats have a neurological disease as a predominant clinical feature
- Neurologic disorders seem to be FIV stain dependent
- Central or peripheral manifestation:
- Ex twitching of the face and tongue, compulsive roaming, dementia, loss of bladder and rectal control, disturbed sleep pattern, ataxia, seizures, intention tremors
- Can be caused by opportunistic infections
- toxoplasmosis, cryptococcosis, FIP
55
Q
How is FIV diagnosed?
A
- Mainly for the detection of antibodies
- Abs for viral structural proteins like transmembrane glycoprotein (gp40), matrix protein (p15) and capsid protein (p24)
- ELISA, Western Blot, IFA
56
Q
Why do diagnostics for FIV not target antigens?
A
- Low viremia during asymptomatic phase
- PCR/RT-PCR may not detect all field viruses
57
Q
What should be done if the screening test for FIV is positive?
A
- If cat is >6mo confirm with another test
- If cat is <6 months retest every 1-2 months until negative or cat is > 6 months
- If cat has unknown vaccination history or is vaccinated confirm with a validated PCR test
58
Q
Why do we perform FIV screening tests prior to vaccination?
A
- No current Ab-based test can differentiate natural FIV infections from FIV vaccine - ALWAYS test before vaccination
- Antibodies due to vaccination persist > 1 year
59
Q
How can FIV be prevented/controlled? (besides vax)
A
- Test and identification
- Sanitize
- Keep FIV+ cats indoors
- minimize transmission
- minimize exposure to other infectious agents
- Neuter
- minimize stress
- Check proviral status of blood donors
60
Q
What is the FIV Vaccination?
A
- Inactivated vaccine: Fel-O-Vax FIV (subtypes A & D)
- Limited efficacy due to genetic diversity of FIV
- Not a core vaccine
- Not a DIVA vaccine
- Only for cats at high risk of infection - ID vaccinated status
61
Q
Compare and Contrast FeLV and FIV on the following points:
Tumors
Bone Marrow Suppression
Neurologic signs
Immunodeficiency
Immune-mediated
Stomatitis
A
