L73 Flashcards
Which are the alpha herpes viruses? Why are they grouped together?
HSV 1 & 2
VZV
All neurotrophic
Which are they lymphotrophic herpes viruses? What disease can all of these viruses cause?
CMV
EBV
HHV 6
Can all cause mono
Compare & contrast lympo vs neurotrophic viruses.
BOTH can infect epithelium
Only lympho can infect lymphocytes/other immune cells
Name the 4 structural aspects of CMV that you need to know (think inside –> out).
LARGE dsDNA genome
Capsid
Tegument
Envelope
What are the 3 categories of CMV genes?
IE - immediate early
E
L
IE genes:
Need protein synthesis?
Fxn
Where & when in cell
DON'T need protein synthesis Gene products fxn in viral DNA synthesis Detected: - Nucleus - 1st (12-20 hrs post infection)
E genes:
Need protein synthesis?
Fxn
Where & when in cell
Need protein synthesis to create gene products
–> fxn in DNA replication + viral protein mod
Detect:
- Cytoplasm
- Nucleus
L genes:
Fxn
Where & when in cell
Gene products = structure
Cytoplasm
Nucleus
Last - 48hrs post infection
What genetic material is found in CMV’s tegument? What does it code for?
4 mRNAs
Code own IE, E & L genes
Code microRNAs
What do microRNAs do?
Control viral & cellular gene expression
What are the 3 types of infection timeframes that CMV can have?
Permissive = lytic infection
Latent
Persistent
Which tissue & cell type is permissive CMV found in?
Epithelial cells
Macrophages
Which cells is latent CMV in?
Hemopoietic cells (in bone marrow & liver)
Which cells is persistent CMV in?
Lymphocytes
Endothelial cells
Bone marrow stroma
Which pt populations are you concerned about for CMV?
Babies - common cause infectious birth defects
IC pts - 1ary or 2ary infection
If compromised, lacking which form of immunity is most likely to cause CMV activation/infection?
CD8
Aka CD8 is most important for keeping CMV from reactivating
Why do you think about CMV in transplant pts?
CMV+ recipient could receive another strain from the donor
Recipient IC - can’t fight off new strain
How can CMV be transmitted?
Most impt:
- Blood transfusions (if right CMV filter not applied)
- Bone marrow or solid organ transplant
Which transplant is the exception to CMV concerns?
Bone marrow - replacing entire immune system including previous immunity!
Most common CMV presentation?
Asymptomatic
CMV diseases in normal pts
Mono - won’t agglutinate
Idiopathic thrombocytopenic purpura
Hemolytic anemia
Hepatitis
CMV diseases in IC pts
MOST ORGAN SYSTEMS Retinitis Hepatitis Gasteroenteritis Colitis Pna Glomerulopathy Disseminated disease
Describe CMV pna CXR
“Polar bear in snow storm”
What cells will you see in CMV biopsy?
Owl’s Eye Cell - BIG epi cells
- Lungs
- GI (colitis)
- Kidneys
What is a distinctive characteristic of CMV in lesions?
Hemorrhage
Describe CMV retinitis
- Micro-infarcts = white dots (not specific to CMV)
2. Progress to hemorrhagic (“ketchup on scrambled eggs”)
What brain/neural pathology might you see in CMV infection?
Periventriculitis = inflammation around ventricles in brain
- Also seen in HHV 6
Transverse myelitis/peripheral neuropathy
Hearing lose = CN8 involvment
Which CMV disease is specific to babies? Symptoms.
Cytomegalic inclusion disease of the newborn
- Microephaly
- Mental retardation
What is the immune response to CMV?
Abs & cell mediated (CD4, 8, NK)
Diagnose CMV
= measure replication levels 1. PCR 2. Histopath/immunocytochem Other - Shell vial = rapid culture
What does Shell Vial rapid culture measure?
Abs vs IE & E antigens
How do you filter CMV out of blood?
Exclude cells w/ buffy coat
Drugs for CMV prophylaxis
Ganciclovir
Valgan
(Acyclovir)
Antiviral to treat CMV
Ganciclovir vs Foscarnet - Use the other if resistent Valgan (retinitis) Cidofovir (retinitis only) Hyperimmune globulin - in combos
Ganciclovir tox
Bone marrow
Foscarnet tox
Renal (not if Cr
How do you get ganciclovir (& valgan) resistance?
- (most likely) UL 97 mutation = CMV kinase
2. UL 54 mutation = DNA pol