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194 Cards in this Set
- Front
- Back
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What is atherosclreosis?
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Gradual, decades-long blockage of (typically) the coronary arteries, aortic arch, other vessels
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What are (4) functions of blood vessels?
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-Blood compatible container
-Selectively impermeable barrier -Monitors and trasnduces blood-borne signals -Integrates the local pathophysiologic mileu |
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What is an example of how blood vessels integrate the local pathophysiologic milieu?
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Clotting only at cut sites and not widely throughout the body
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What are the three layers of the blood vessel?
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-Intima
-Media -Adventitia |
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What is the intima made up of?
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-Layer of endothelial cells
-Elastica interna |
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What is the media madwe up of?
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Smooth muscle cells - involved in contraction relaxation of vessels to regulate blood flow
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What is the role of the adventitia?
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CT that provides support for blood vessels
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What is a normal artery like?
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Thin intima
Scant leukocyte population Little expression of adhesion proteins or cytokines No microvessels |
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What are coronary arteries?
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They feed the heart tissue with oxygenated blood
Originate from the aorta |
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What is a myocardial infarction?
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A block in blood flow to a part of the heart and the tissue will die as a result of not getting any oxygenated blood
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What are some anti thrombotic factors produced by endothelial cells?
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TPA, prostacyclin, thrombomodulin
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What are some pro thrombotic factors produced by endothelial cells?
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Coagulation factors, tissue factors,
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What are some vasorelaxors produced by endo cells?
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Nitric oxide, prostacyclin
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What are some vasoconstrictors produced by endothelial cells?
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Endothelin 1, angiotensin II
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What are some growth inhibitors produced by endo cells?
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Nitric oxide, TGF-beta
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What are some antiinflammatory molecules produced by endo cells?
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Nitric oxide, prostacyclin
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What are some proinflammatory molecules produced by endo cells?
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Cytokines (IL-1beta, MCSF)
Chemokines (IL-8, MCP-1) ICAMS, Selectins |
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What type of stimulation does endothelium respond to?
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Biochemical
Biomechanical |
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What are some biochemical factors that endothelial cells respond to?
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Hormones, growth factors, cytokines, bacterial products
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What are biomechanical factors that endo thelial cells respond to?
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Wall shear stress, pressures, cyclin strains
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What is wall shear stress?
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Acts along blood flow
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Wha pressures do endothelial cells pace?
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Perpendicular to blood flow
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What are cyclic strains?
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In response to the heart beat
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What is the normal blood pressure?
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120/80
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Where do atheromas form?
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In regions of DECREASED shear stress
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How do regions of low shear stress contribute to atheroma formation?
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In areas of decreased shear stress, the endo cells are not as perfectly lined up and create regions of disrupted flow
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What are some risk factors for atherosclerosis?
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Hypertension, smoking, hypercholesterolemia, diabetes mellitus
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What are some causes of atheroma formation?
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Low eNOS
Less endothelial repair Decreased cytoskeletal/cellular allignment in direction of flow Increased ROS Increased lipoprotein permeability Increased inflammation |
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In what area of a curved, healthy artery is a plaque likely to form?
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The inner curve- where low shear stress is located
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What is the outer curve referred to as?
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Plaque-free wall
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What happens to the PFW when ana theroma forms on the inner curve?
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It thickens - adaptive remodelling to maintain the difference in shear stress between the outer and inner curve
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How can this "balance" of adaptive remodelling be broken to get thrombosis?
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The increased tensile strength at the lateral plaque shoulders can lead to fissurinr, damage, expore of SM and thus thrombosis
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What type of knockout mouse is more susceptible to developing large amoutns of fatty deposits when fed a high fat diet?
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ApoE knockout mice
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What constitutes the plaque core?
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Cell debris from apoptosed foamy cells, matrix constituents degraded by MMPs
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What can macrophages take up to become foamy cells?
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OxLDL
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Which cells produce TF?
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Smooth muscle
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What are key causes of endothelial dysfunction in atherosclerosis?
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Disturbed flow
Inflammatory cytokines OxLDL Advanced glycosylation end products Homocysteine |
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What effects do these deregulated cell processes have on endo cells?
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-Increased prothrombotic activity
-Impaired vasorelaxation -Increased permeability and trapping of LDL -Smooth muscle cell migration, proliferation and ECM production -increased leukocyte recruitment |
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What effect would altered junction and transport result in?
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Chemicals and or cells (that arent supposed to) get through the endothelial layer - would cause recruitment of macrophages to try and eliminate these abnormal substances
-Also increased permeability and trapping of LDL |
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Circulating mediators, like cytokines, are everywhere - why arent endothelial cells activated everywhere?
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Need biomechanical AND biochemical stresses
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Where are most atherosclerotic plaques found?
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Near vessel junctions where there is tumbling and turbulent blood flow
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When does endothelial-leukocyte adhesion occur?
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Early in atherogenesis
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What causes the endothelial-leukocyte adhesion?
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Expression of an array of adhesion proteins on surface of endothelial cells, like VCAM, ICAM-1 and P-Selectin
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Which leukocytes are typically recruited in atheroma formation?
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Monocytes/macrophages
T cells, B cells, Granulocytes, eosinophils, mast cells |
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What are classical features of a generic chronic inflammation?
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-Monoleukocytes (adherence, penetration, accumulation)-
Fibroblast proliferation (produce ECM and collagen) -Collagen accumulation -Angiogenesis |
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What are features of atherosclerosis?
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-Monoleukocytes (adherence, penetration, accumulation)
-Smooth muscle cell proliferation and dedifferentiation -Neoangiogenesis -Lipid accumulation -Calcification -Thrombosis |
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What happens as a result of SMC dedifferentiation?
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Secrete more ECM, more collagen and MMP (damaging enzymes!!)
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What is so problematic about lipid accumulation?
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Lipids are very prothrombic - platelets adhere leading to thrombosis
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Which family does Cytomegalovirus belong to?
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Herpes!
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What type of genome does CMV have?
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dsDNA, >200 ORF
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What type of infection does CMV cause?
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Widespread, opportunistic
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What is the prevalence of CMV?
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In people >35 yrs old, 80% are positive for CMV
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Are the important cells in atherosclerosis development susceptible to CMV infection?
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Both smooth muscle cells and endothelial cells are permissive for CMV infection
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What are some consequences of CMV infection of endothelial cells from the heart?
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-Increased adhesion molecule expression
-Increased chemokine synthesis -Increased chemoattractant synthesis |
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What are some adhesion molecules that are expressed upon CMV infection of endothelial cells?
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ICAM, VCAM, and P-selectin
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What are some chemoattractants that are synthesized as a result of CMV infection?
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IL-8, MCP-1
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What is the different between post-transplant atherosclerosis and atherosclerosis?
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Occur quicker, patients are immunosuppressed
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What is some epidemiological evidence of CMV role in atherosclerosis?
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CMV-positive patients did worse than CMV-negative patients when receiving a CMV-positive heart
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What evidence did the effect of anti-CMV treatment have?
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Treatment with gancyclovir, valganciclovir, anti-CMV Abs decreased vasculopathy and increased survival
SHOWS that reducing viral activity may reduce problems and promote survival |
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What effect did acute CMV infection have on a new, transplanted heart?
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-Increased macrophages, CTLs in cardiac vessels
-Increased EC proliferation and intima thickening -CMV E and L protein positive -Infectious CMV isolated SHOWS acute CMV infection impacts a new heart |
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What was the difference when hearts from an acutely infected vs. latently infected animal were given to a CMV neg mouse?
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ACUTE: infectious virus in both hearts, liver, spleen, salivary glands. Anti-CMV Abs
LATENT: Spleen and salivary glands. Anti-CMV Abs |
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What was the difference when mice were treated with immunosuppressive drugs before receiving hearts from acute vs. latently infected mice?
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Both DIED and High titers of CMV were isolated from all organs in both cases
SHOWS - immunosuppression is key to how virus attacks these hearts- shwo swhy heart disease may develop so quickly in post-transplant patients |
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What does use of irradiated CMV show?
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Time for rejection is same as uninfected mice - shows CMV action is requried to reduce rejection time - CMV presence is not enough to speed up rejection
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What happened when ApoE-/- mice were given high dose CMV?
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-Aggravated atherosclerosis lesion progression
-Rise in circulating IFNgamma and TNFalpha (systemc immune response) |
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What was the difference between athero lesion area in uninfected vs. irrad CMV vs. CMV?
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Infection lesion number was the same, but the area was increased in both UV CMV and CMV - shows the imporance of the local inflammatory effect in lesion area
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Which molecules are increased in CMV infection?
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Increased IFN-g, increased IL-6, increased MCP-1
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What is the role of increased MCP-1 in atherosclerosis?
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May attract monocytes to atherosclerotic lesions
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How does CMV infection, IFNg, IL-6, MCP increase play a role in atherosclerosis?
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CMV infects endothelial cells, causing them to produce IL-6 and IFN-g, resulting in an increase in MCP-1 and thus increased adhesion of monocytes to lesion site -> promotion of atherosclerosis
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How does reactivation of CMV contribute to atheroscleroris?
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Promotes inflammation - causes recruitment of immune cells liek T cells and monocytes. Monocytes may ingest fat and become foam cells, die, causing an even bigger inflammatory reaction - and the plaque gets bigger and bigger!
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What is angioplasty?
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Widening an obstructed vessel
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What is restenosis?
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When plaques come back after they are removed
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What is the difference between restenosis and atherosclerosis?
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-Injury during restenosis procedure is ACUTE (wherease atherosclerosis takes years)
-Different coures and pathology |
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How does the injury arise in restenosis?
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During the angioplasty procedure - endothelial cells are removed. As a result, the udnerlying smooth muscle cells lack the proection the endotheial cellsprovde -leading to clot formation and SMC prolfieration
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What happens to the SMC in the first 3-6 months?
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SMC dedifferentiate and migrate from the media to the neointima.
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What form does the SMC become?
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Contractile to synthetic - > they make ECM
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What does the secreted ECM form?
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The fibrous cap that underlies the endothelial cells -creates the buldge - obstructs flow
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What is a MAJOR difference between restenosis and atherosclerosis?
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More SMC accumulation in restenosis
No FOAM OR LIPID ACCUMULATION |
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What is a treatment device for restenosis?
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A stent
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What is the problem with using a stent to treat restenosis?
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Doesnt last forever
Thrombus formation can occur on the stent and SMC can grow around the stent |
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How can one prevent the problems associated with stents?
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Coat the stents with anti-proliferation
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What are some patient data to associate CMV with restenosis?
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-30-75% of lesions with restenosis contain CMV
-SMC are CMV antibody positive -CMV seropositive patients have: -Decreased luminal diameter - Increased rate of restenosis |
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What was a rodent study to show that CMV promotes restenosis?
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-CMV infected rodents has increased formation of neointima
-CMV was isolated from salivary glands and spleen -Increased circulating IL-2 and IL4 -Therefore CMV promotes restenosis + inflammation |
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How does CMV associate with platelets?
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Human pulmonary artery endothelial cells infected with CMV showed increased platelet aggregation- and this was reduced with UV-irad CMV - therefore CMV action is required for platelet aggreagation
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What is another piece of evidence (besides using UV-irrad CMV)?
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Treating with antivirals resulted in reduced platelet adhesion
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What was the evidence that CMV stimulates SMC migration?
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Found that CMV infection specifically induces SMC migration of arteries and not SMC from veins
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What is the model of CMV action in restenosis?
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CMV infection of SMC in arteries causes SMC proliferation, release of molecule slike RANTES and MCP-1, and subsequent plaque formation
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What is myocarditis?
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Inflammation of heat muscle
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What do patients with myocarditis develop?
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Dilated cardiomyopathy
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What is the difference between a heart with dilated cardiomyopathy and a normal heart?
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-Walls are same thickness
-Cavity of LV is dilated - more globular shape (less cone shape) |
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What are some manifestiations of the dysfunctioning dilated heart?
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-Does not pump blood as well as normal
-Interior diameters are larger -Fractional shortening is reduced (normal = 60%) |
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What is Cocksackie B virus?
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Picornaviridae member, enterovirus
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What is the natural tropism of Coxsackie B virus?
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Gut, epithelial cells, immune cells, neurons, cardiomyocytes
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How big is the genome for Coxsackie B virus?
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7.4 kb + strand RNA
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What are the viral proteases?
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2A and 3C
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What is the receptor for CVB3 entry?
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CAR (Coxsackie adenovirus receptor)
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Where is CAR located?
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Intercalated disks of cardiomyocytes
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What is the co-receptor for CVB3?
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DAF (Decay accelerating factor)
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What are three time periods of myocarditis?
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Acute
Subacute Chronic |
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What are some characteristics of acute myocarditis?
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-Myocyte necrosis
-Macrophage activation, cytokine release, inflammatory response -Can isolate CVB3 from serum of patient |
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What are some characteristics of subacute myocarditis?
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May or may not be able to isolate virus
-Immune response is clearing virus (NK cells, lymphocytes, monocytes, etc) |
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What are some characteristics of chronic myocarditis?
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FIbrosis
Cardiac dialation Heart failure |
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When does myocarditis develop?
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When the balance between viral clearing and myocyte damage is not normal (ineffective viral clearing or overaggressive immunological activation)
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What determines the development of chronic myocarditis or clearance of virus?
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-No correlation between viral replication and inflammation
-Correlation with higher circulating levels of cytokines and inflammation in the hearts |
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What does this show?
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The difference in RESPONSE to infection may be responsible for differences in outcomes
i.e. a higher proinflammatory response may be associated with damage and chronic myocardititis |
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Is IFN response important?
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Deletion of type I receptor was more detrimental than type II- therefore type I IFN may be important in reducing CVB3 infection in the hearts
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What happens when you suppress the response TOO much? eg. by overexpressing the negative regulator SOCS3
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Mice are worse off- Therefore need a balance!
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What does SOCS3 regulat?
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JAK/STAT activation (induced by molecules like IL-6)
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How can you ensure you overexpression of SOCS only in heart cells?
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Combine with alpha-MHC (myosin heavy chain)
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What is CVB3 protease 2A?
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Cysteine endopeptidase that cleaves proteins involved in heart function
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What crucial protein does CVB3 protease 2A cleave?
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Dystrophin-sarcoglycans complex
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What is a result of cleaving the dystophin complex?
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Loss of sarcolemmal integrity and heart failure
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What happens when 2A was expressed in the heart (using a transgene)?
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Chamber sizes increased (dilated cardiomyopathy)
Fractional shortening is reduced Sarcolemmal membrane integrity reduced -Expression of 2A alone induced dialted cardiomyopathy!! |
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What do we see in the late phase of myocarditis?
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Heart-muscle specific autoantibodies and inflammatory infiltrates (lymphoctes + macrophages) into the heart
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Why do autoantibodies develop in late stages of myocarditis?
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Cardiomyocytes are damaged and there is the release of muscle proteins that are rarely seen by the body
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Why is it difficult to link infection to development of autoantibodies to myocardial dysfunction?
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-Signs of infection may appear days after actualy infection
-Clinical confrimation of autoimmunity is only apparent during late stage -Virus cleared by this point |
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How to show that antibodies against HEART muscle proteins results in myocardititis?
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T cells + spleen cells from mice with active myocarditis and injected into naive mice
-Saw development of myocarditis (immunological and pathological features seen like w/ CVB3 infection) -Not seen with skeletal muscle myosin |
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What is EAM?
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Experimental autoimmune myocarditis
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What are the two isotypes of myosin heavy chain in mice?
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ALpha and beta
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Which isotype is predominant in the heart and implicated in cardiac difficulties?
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MHC alpha
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Which myosin heavy chain results in cardiac myocarditis?
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MHCalpha
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What sequence is required for myocarditis?
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XXXMAXXXSTXXX - a basic sequence!
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Can injecting this peptide alone result in development of myocarditis? I.e. via molecular mimicry?
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No - for instance a similar peptide isolatd from T. cruzi did not result in development of myocarditis.
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What does this mean?
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THis motif is NECESSARY for myocarditis but it is not the ONLY feature required
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What did transgenic mice overexpressing type I interferon showed?
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Tg mice survived a lethal dose of CVB3, titer of heart-specific antibody was lower - therefore protection from myocarditis in Tg mice was a consequence of reduced viral replication in pancreas and reduced spread to heart
SHOWS that viral infection + molecular mimicry are some of the requirements |
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What happens when Tregs alone were infused in mice that had a transplanted human artery?
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Reduced wall thickening - so REDUCTIONS IN EFFECTOR FUNCTION AND GRAFT INFILTRATION INHIBIT TRANSPLANT LOSS. If you suppress inflammation you get less myocardittis
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Therefore, what are the THREE components required for myocarditits development?
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1) Viral replication
2) Molecular mimicry 3) Effector functions of various T cell populations |
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Summarize CVB3 and its involvement in development of myocarditis
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Coxsackie virus bind to receptors, enters, protease chops up into functional parts, protease acts on dystrophin -> results in problems
-Inflammation is infvolved, acquired immunity |
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How does HIV correlate with heart disease?
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HIV + status increased the risk for myocardial infarction and coronary artery disease compared to HIV - people of the same age and risk factors
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What happens with HIV therapy?
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There is INCREASED incidence of MI or stroke
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How can you look at JUST the effects of HIV and not therapy?
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Look at studies done in the pre-HAART era
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How did development of DCM (dilated cardiomyopathy) compare between HIV patients with normal vs. low CD4 levels
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Occurs equally - no matter state of immune system
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How did development of DCM (dilated cardiomyopathy) compare between HIV patients with normal vs. low CD4 levels
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Occurs equally - no matter state of immune system
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How would the cardiac intima media thickness of the carotid artery compare in HIV patietns vs. controls?
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THicker
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How does decrease in heart function compare in HIV+ symptomatic vs asymptomatic individuals?
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The same!
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What are the parameters involved in HIV an heart disease?
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Abnormal EKG waves
Reduced LV ejection fraction Reduced RV ejection fraction |
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Can cardiomyocytes be infected with HIV?
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Yes! - therefore virus can impact directly on heart cells
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How does HIV Tat promote atheroma formation?
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Transfected monocytes produce:
-Increased TNFallpha, NFKB, IL-6 -Increased oxidative stress -Increased VCAM and ICAM -Increased gelatinase -Increased adherence to endothelial cells |
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Why does gelatinase increase cause a problem?
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Destroys fibrous cap of atheromas- leading to plaque rupture, MI and death!
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What would you expect with HIV drug treatment and what is really observed?
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-Expect REDUCTION of CAD and cardiac events if HIV viral load is reduced, BUT we still see MI and CAD with HAART
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What effect do NRTIs have on the mitochondrea
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Decrease RNA pol g activity - results in enlargement of mitochondria in skeletal muscel
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How does risk of MI correlate with protease inhibitor use?
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Increases with increase protease inhibitor use
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What happens when patients went on drug holidays?
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Displayed increased cardiac function
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What risk factors for cardiovascular disease are associated with protease inhibitor use?
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Increased LDL, decreased HDL, diabetes, development of lipodystrophy
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What are physical features of lipodystrophy?
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Buffalo hump, increased abdominal fat, lean face arms and legs
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WHat is associated with the loss of afat in arms and legs after PI use?
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Decreased differentiation of adipocytes
Increased apoptosis of adipocytes |
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What does cardiac disease in SIV infected Rhesus macaques indicate?
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Poor prognosis than infected w/o heart disease
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How can you test if HIV is expressed in cardiomyocytes?
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Attach HIV LTR to a CAT reporter gene
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What happens when TAT was expressed ONLY in cardiomyocytes?
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Cardiac hypertrophy, decreased LV fractional shortening, enlarged mitochondria (dysfunctional)
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What happens when NEF is expressed inly in cardiomyocyteS?
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Nothing - shows specificalyl Tar is necessary to induce pathology
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How does drug treatment affect WT or HIV animals?
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Decrease in cardiac function is more severe in HIV patients - treatment + HIV together synergistically cause cardiac failure!
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How can HIV adversely affect the vasculature? (7)
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1) Endothelial dysfunction
2) Lipid disorders 3) Endothelial activation 4) Systemic inflammatory cytokine/chemokine dergulation 5) HIV infection of SMC and endo cells 6) Enhanced atheroma formation by activated macrophages 7) prothrombic state |
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How does ART adveserely afefct the vasculature? (9)
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1) Endothelial dysfunction
2) Increased endothelial permeability 3) Increased oxidative stress 4) Increased mononuclear cell adhesion 5) insulin resistance 6) accelerated lipid accumulation in cell wall 7) persistent inflammation and immune activation 8) impaired response to vascular injury 9) ART-associated lipodystrophy |
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What does ART-associated lipodystrophy lead to?
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Metabolic disorders, increased systemic inflammation, and reduced circulating adiponectin
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What happens when HIV+ mothers transfer to their childreN?
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-Structure is fine
-Functional defects: cardiac pumping is reduced.. fractional shortening is reduced, heart rate is faster, heart size is larger w/ reduced contractility |
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What is teratogeness?
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the development of defects in an embryo
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What are Wilson's 6 principles of in utero vulnerability?
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1) Susceptibility to a teratogen depends on the genotype of the fetus and how it responds to its environment
2) Susceptibility depends on the developmental stage 3) Teratogens are specific 4) Factors can influence the adverse effect (route, amount rate of transfer) 5) 4 outcomes: death, malformation, growth retardation, functional defect 6) Effect increases with increased frequency and dose (no effect -> lethality) |
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What are some examples of teratogenic agents?
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-Drugs and medications
-Environmental chemicals -Ionizing radiation -Metabolic imbalances -Infections |
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What are some examples of infectious teratogenic agents?
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Rubella
Cytomegalovirus |
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What does TORCH stand for?
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Toxoplasmosis, Other agents, Rubella, CMV, HSV
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What is Rubella?
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Togavirus, enveloped, single stranded RNA genome
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How does entry of Rubella occur?
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Via internalization in an endosome
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What can happen if the mother is infected with RUbella within the first 20 weeks of pregnancy?
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The child ma ybe born with congenital rubella syndrome (CRS)
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When is the neural tube sensitive to developing defects?
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Very early on in development
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When is the heart sensitive to developing defects?
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6-8 weeks after conception
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What are some congenital defects that arise in tCRS when the mother is infected in the first trimester?
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Ocular, cardiovascular, CNS, deafness, growth retardation
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What are some congenital defects that arise when the mother is infected with rubella in the second trimester?
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Deafness, retinopathy, microcephaly, mental retardation
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What are some congenital defects that arise when the mother is infected in the third trimester?
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Growth retardation
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Why is the baby so susceptible to defects if the mother is infected early on in gestation?
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The fetus does not have cell-mediated or humoral immune defenses until around the 20th week of gestation
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What is the CRS "triad"?
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Deafness
Eye abnormalities COngenital heart defectsq |
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Why do cataracts develop in CRS fetuses?
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AS rubella infects the embryonic lens, it slows cell division and maturation
-Causes degeneration of lense fibers - becomnig opaque! |
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What are some heart abnormalities that can develop in CRS fetuses/
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Patent ductus arteriosis
Ventricular septal defects Pulmonary artery stenosis Pulmonary artery hypoplasia |
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What is Patent ductus arteriosis?
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The ductus arterosis is between the pulmonary artery and aortic arch and allows fetus blood supply to bypass the lungs. It closes usually 12-24 hrs after opening
-In CRS it may not close properly! |
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What is ventricle septal defect?
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Some blood goes from the LV into the RV -> more pressure on the LV, cuaing increased pressure in RV - development of pulmonary hypertension
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What is pulmonary artery stenosis?
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When the pulmonary artery narrows - blood through thorugh narrow opening is not as effective
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What can one observe in aborted infected fetuses?
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Damage in multiple sites - eyes, heart, brain, ears
Swelling of mito and dilation of ER |
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How does infection from the mother to fetus occur?
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In the intervillous space the virus gets transferred from maternal to fetal blood
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What are the NUCLEAR mechanisms of Rubella teratogenecity?
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RV p90 binds retinoblastoma protein (tumor suppressor in retina cells) -> induce altered growth
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What are the MITOCHONDRIAL mechanisms of Rubella Teratogenecity?
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-Capsid proteins associate with mito -> decreased ATP production
-Mitochondria become abnormally shaped -> growht retardation (need energy for development) |
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What are the CYTOSKELETAL mechanisms of Rubella teratogenecity?
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Actin depolymerization
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What are the organs like of CRS infants?
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Smaller, fewer cells, depressed mitotic activity, slow cell divison, inhibition of development of organ precursor cells
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Where does CMV cause congenital defects?
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The CNS
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What are symptoms of congenttal CMV infection?
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5-10% develop:
-Microcephaly -Periventricular calcification (brain ventricles) -Cerebellar hypoplasia -Eye abnormalities (e.g micropthalmia) -Optic nerve atrophy |
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What is a necessary step for transmission of CMV infection to fetuses?
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CMV infection of the placenta
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Decribe process of development of embryo
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-Oocyte + sperm
-Two cell embryo -4 cell embryo -Blastocyts, once hatched its components become whats in brackets: -Inner cell mass (embryo) -Trophoblasts (placenta) |
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What is the zonae?
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At all stages pre-hatching - the embryo is enclosed in this
It keeps the embryo the same size despite cells dividing and contains the sperm receptor |
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Is the early embryo susceptible or resistant foto CMV infection?
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Yes - seen with other viruses too!
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What might be a reason for why the early embryo is resistant to viral infection?
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-Fetus relies on maternal protein synthesis from maternally stored RNA until 4-cell stage
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What does LIF (Leukemia inhibitory factor) do?
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Keeps embryonic stem cells in an undifferentiated stat
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At what point do ES cells become susceptible to CMV infection?
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Only when differentiated!
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Which cells were most susceptible to CMV infection following differentiation?
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Glial cells (not neurons!)
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Why arent blastocysts susceptible?
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As mentioned - they have a transcriptional block. Only find infection once blastocysts hatches and cells differentiate -c an find infection in placenta and mesoderm cells!
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What happens to brain susceptibility to CMV with age?
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Declines with age
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Why, if CMV doesnt infect neurons directly, are neurons impacted?
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CMV infect and kills glial cells. Glial cells serve to support neurons and therefore in CMV infection the neurons are secondarily affected because they dont get the support they need to develop normally.
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Sum up in one sentence when CMV infects cells
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Post implantation but after differentiation
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