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Virology > FeLV and FIV > Flashcards

FeLV and FIV Flashcards

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
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
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
  1. Acute infection
  2. asymptomatic carrier (clinical latency)
  3. 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

Virology (37 decks)

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