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Virology Final > Viruses and the Cardiovascular System > Flashcards

Viruses and the Cardiovascular System Flashcards

1
Q

Cardiopathic Viruses-Myocarditis and Coxsackie B virus

A
  • CVB3 and inflammatory heart disease (myocarditis) in humans and animals
  • evidence for autoimmune response against cardiac antigens (cardiac myosin and mitochondrial adenine nucleotide translocator protein (ANT) protein)
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2
Q

Cardiopathic Viruses-Congenital Rubella

A
  • combo of fetal abnormalities
  • common defect is heart damage
  • virus appears to spread through vascular system of fetus (through the placenta)
  • teratogenic
  • incidence has dropped since advent of vaccine (1969)
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3
Q

Hemorrhagic Viruses

A

Flavi-dengue, yellow fever
Arena-lassa fever
Bunya-rift valley fever, Crimean Congo hemorragic fever, Hantaan
Filo-Ebola, Marburg

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4
Q

Flaviviridae

A
  • 8 antigenic complexes (70 viruses)
  • transmitted by insects
  • viruses cause varying diseases from hemorrhagic infections to encephalitis
  • visceral disease-disease of internal organs
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5
Q

Dengue Virus Genome

A

-mRNA translated to produce polyprotein which proteolytically cleaved

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6
Q

Transmission and early events in dengue virus infection

A
  • use mosquito to penetrate lower skin layers
  • viruses become free in circulation
  • viruses target WBC
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7
Q

Dengue Virus and Pathogenesis

A

4 serotypes of virus (D1-4)
2 types of disease:
-dengue fever-relatively mild, most infections
-severe disease (dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)), less common, 1% of dengue infections

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8
Q

Risk factors for severe dengue disease

A
  • prev. infection w/ heterologous serotype
  • maternal antibodies
  • passive immunization
  • antibody dependent enhancement (ADE)!!-mediated by sub neutralizing Ab’s and Fc receptor bearing cells, ADE amplifies vrep and prod. of cytokines/chemokines
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9
Q

Characteristics of Severe Dengue Disease (5)

A
  1. vascular permeability
  2. thrombocytopenia
  3. complement activation
  4. activation of coagulation pathway
  5. T cell activation
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10
Q

Characteristics of Severe Dengue Disease-vascular permeability

A
  • reg. by endothelial cells
  • possible mediators: TNF, IL-1, vascular endothelial growth factor (VEGF), histamine, lipid mediators (PAF, leukotrienes, thromboxanes), anaphylotoxins
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11
Q

Characteristics of Severe Dengue Disease-thrombocytopenia

A
  • some evidence for block in megakaryocyte maturation
  • platelet half life reduced
  • platelet fxn deficiencies
  • dengue immune complexes detected on platelets (may target platelets for destruction in spleen)
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12
Q

Characteristics of Severe Dengue Disease-Complement Activation

A

-decreased C3
-evidence for activation of both classical and alternative pathways
-anaphylatoxins (C3a and C5a) and soluble terminal complement complexes (SC5-9)
Consequences of prod of anaphylatoxins:
-increase vascular endothelial cell permeability
-platelet deposition
-increase leukocyte chemotaxis (C5a)
-activate mast cells

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13
Q

Characteristics of Severe Dengue Disease-Activation of Coagulation Pathway

A
  • decreased fibrinogen levels
  • increased fibrinogen degradation products
  • leads to exhaustion of factors required for blood clotting
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14
Q

Characteristics of Severe Dengue Disease-T cell activation

A
  • dengue virus specific T cells stimulated by dengue Ag to produce IFNgamma
  • IFNgamma upreg. FcgammaR and increases ADE
  • dengue virus specific T cells (either CD4+ or CD8+) lyse virus infected target cells in HLA restricted manner
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15
Q

Host Genetics and Susceptibility to Severe Dengue Virus (Variance in MICB gene)

A
  • major MHC-1 polypeptide related sequence B
  • encodes activating ligand for NKG2D type II receptor on NK and CD8+ T cells
  • ligation of NKG2D by MICB stimualtes antiviral effector functions in NK cells, including cytokine expression and the cytolytic response
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16
Q

Host Genetics and Susceptibility to Severe Dengue Virus (Variance in PLCE1 gene)

A
  • phospholipase C epsilon 1
  • also implicated in kidney disorder
  • dysfunction of the glomerular basement membrane results in proteinuria and hypoproteinemia that can lead to reduced vascular oncotic pressure and edema
  • some similarities w/ severe dengue
  • suggests role for PLCE1 in maintaining normal vascular endothelial barrier fxn
17
Q

Ebola Viruses (5)

A
  • zaire (frequent outbreaks, 2014)
  • sudan
  • cote d’ivoire
  • uganda bundibugyo
  • reston (philippines to USA, non pathogenic for humans)
18
Q

Ebola Pathogenesis

A
  • infects lymph node, liver, adrenal gland
  • transmitted by blood
  • IL8, TNFalpha, NO are vascular mediators released by monocytes, cause vascular leakage

Virology Final (7 decks)

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