Viruses and the Cardiovascular System Flashcards
Cardiopathic Viruses-Myocarditis and Coxsackie B virus
- 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)
Cardiopathic Viruses-Congenital Rubella
- 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)
Hemorrhagic Viruses
Flavi-dengue, yellow fever
Arena-lassa fever
Bunya-rift valley fever, Crimean Congo hemorragic fever, Hantaan
Filo-Ebola, Marburg
Flaviviridae
- 8 antigenic complexes (70 viruses)
- transmitted by insects
- viruses cause varying diseases from hemorrhagic infections to encephalitis
- visceral disease-disease of internal organs
Dengue Virus Genome
-mRNA translated to produce polyprotein which proteolytically cleaved
Transmission and early events in dengue virus infection
- use mosquito to penetrate lower skin layers
- viruses become free in circulation
- viruses target WBC
Dengue Virus and Pathogenesis
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
Risk factors for severe dengue disease
- 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
Characteristics of Severe Dengue Disease (5)
- vascular permeability
- thrombocytopenia
- complement activation
- activation of coagulation pathway
- T cell activation
Characteristics of Severe Dengue Disease-vascular permeability
- reg. by endothelial cells
- possible mediators: TNF, IL-1, vascular endothelial growth factor (VEGF), histamine, lipid mediators (PAF, leukotrienes, thromboxanes), anaphylotoxins
Characteristics of Severe Dengue Disease-thrombocytopenia
- 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)
Characteristics of Severe Dengue Disease-Complement Activation
-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
Characteristics of Severe Dengue Disease-Activation of Coagulation Pathway
- decreased fibrinogen levels
- increased fibrinogen degradation products
- leads to exhaustion of factors required for blood clotting
Characteristics of Severe Dengue Disease-T cell activation
- 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
Host Genetics and Susceptibility to Severe Dengue Virus (Variance in MICB gene)
- 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
Host Genetics and Susceptibility to Severe Dengue Virus (Variance in PLCE1 gene)
- 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
Ebola Viruses (5)
- zaire (frequent outbreaks, 2014)
- sudan
- cote d’ivoire
- uganda bundibugyo
- reston (philippines to USA, non pathogenic for humans)
Ebola Pathogenesis
- infects lymph node, liver, adrenal gland
- transmitted by blood
- IL8, TNFalpha, NO are vascular mediators released by monocytes, cause vascular leakage
