FeLV and FIV Flashcards

(61 cards)

1
Q

What Family and Genus do FeLV and FIV belong to?

A
  • Family: retroviridae
  • Genus: Gammaretrovirus (FeLV)
    • Lentivirus (FIV)
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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
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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
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4
Q

How stable is FeLV?

A
  • Fairly unstable in dry environment - few hours
  • Inactivated by commonly used disinfectants
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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
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6
Q

What is the Pathogenesis of FeLV?

A
  1. Oral/nasal contact with virus
  2. Replication in Tonsil and Local lymphoid tissue
  3. Mononuclear leukocyte-associated viremia
  4. Replication in systemic lymphoid tissues
  5. Replication in Bone Marrow Megakaryocytes and Granulopoietic cells and in intestinal crypt epithelium
  6. Marrow-Origin viremia PMN’s and Platelets (FeLV IF test +)
  7. infection of mucosal and glandular epithelium
  8. Leukemogenesis or Aplasia
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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
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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
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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
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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
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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
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12
Q

What cells does the Degenerative disease of FeLV form?

A
  • Lymphoid cells
  • Bone Marrow
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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)
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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
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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)
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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
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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
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18
Q

What is FeLV-induced oncogenesis?

A
  • FeLV causes malignancy by randomly inserting FeLV genome near a cellular proto-oncogene
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19
Q

What is Feline induced lymphoma?

A
  • 4 types based on their most frequent anatomic locations
    • Thymic
    • Alimentary
    • Multicentric
    • Atypical/extranodal
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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
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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
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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
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23
Q

What is FeLV induced Atypical/extranodal lymphoma

A
  • Solitary tumors in kidneys, CNS, eyes, nasal cavity, heart or skin
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24
Q

What are the types of FeLV-induced Leukemia?

A
  • Lymphoblastic leukemia
  • Myeloid leukemia
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25
What is FeLV induced Lymphoblastic Leukemia?
* 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
What is FeLV-induced myeloid leukemia?
* 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
What is Feline Sarcoma Virus (FSV)?
* 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
What is the goal of FeLV diagnosis?
Detect progressively infected cats
29
How is FeLV diagnosed?
* 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
30
Can FeLV be diagnosed with the detection of Antibodies?
* No, not useful * false positives from: * maternal ab * vaccination * Ab endogenous FeLV sequences * Abortive and regressive infections
31
What are the ELISA/immunochromatographic tests for FeLV?
* 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
When should a cat be retested if their initial FeLV test is negative but they had a suspected exposure?
1 - 2 months after the last potential exposure
33
What are the different testing strategies for FeLV?
* 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
What is the prognosis for cats with FeLV?
* 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
How can FeLV be prevented/contolled?
* 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
What Vaccines exist for FeLV?
* 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
What is the recommended vaccination protocol for FeLV?
* 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
What does the FeLV vaccine do?
* Decreases the rate of: * Transient & persistent viremia * Latent infection * Development of FeLV-related diseases
39
What is the structure of Feline Immunodeficiency virus (FIV)?
* 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
What is the prevalence of FIV?
* ~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
How is FIV transmitted?
* Primarily through biting * Blood transfer * mucosal contact * infected queen to kittens * through milk
42
What is the stability of FIV?
* Fairly unstable in dry environment (few hours) * fomite transmission not important * inactivated by commonly used disinfectants
43
What are the cell targets of FIV?
* CD4+ T Cells * Dendritic cells * macrophages * CNS cells
44
What is the staging of a FIV?
1. Acute infection 2. asymptomatic carrier (clinical latency) 3. AIDS-related Complex
45
What is the acute infection stage of FIV like?
* primary viremia * Transient and mild unspecific signs: * Fever (2weeks) * neutropenia (2-4 wks) * gingivitis * enteritis * conjunctivitis * URI * depression * generalized lymphadenopathy (2-9mo)
46
What happens during the latent phase of FIV?
* 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
What happens during the end stage of FIV?
* Feline AIDS - chronic, recurrent diseases * Progressively decreased CD4+ T cells & B cell proliferation ⇢ CD4+ / CD8+ ratios decrease * High circulating viral load * Opportunistic infections
48
What diseases are associated with FIV?
* Immunodeficiency and opportunistic infections * Myelosuppression * Immune-mediated diseases * Tumors * Neurological dysfunction
49
Why is Immunodeficiency and opportunistic infections important in cats with FIV?
* 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
What are the frequent secondary infections in cats with FIV?
* FeLV * FHV * FCV * FIP * Demodex * Cryptococcus * Candida * Isospora * Hemotropic Mycoplasma spp * Pseudomonas * Otodectes * Mycobacteria * others
51
What are the common illnesses of cats with FIV?
* Chronic gingivostomatitis * Fever * Skin abscess * Lymphadenopathy * URI * Ear infections * Weight loss * diarrhea * chronic rhinitis
52
Why are immune related diseases are associated with FIV?
* 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
Why are Tumors associated with FIV?
* 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
Why is neurological disfunction associated with FIV?
* ~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
How is FIV diagnosed?
* 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
Why do diagnostics for FIV not target antigens?
* Low viremia during asymptomatic phase * PCR/RT-PCR may not detect all field viruses
57
What should be done if the screening test for FIV is positive?
* 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
Why do we perform FIV screening tests prior to vaccination?
* 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
How can FIV be prevented/controlled? (besides vax)
* 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
What is the FIV Vaccination?
* 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
Compare and Contrast FeLV and FIV on the following points: Tumors Bone Marrow Suppression Neurologic signs Immunodeficiency Immune-mediated Stomatitis