L73

Question 1

Which are the alpha herpes viruses? Why are they grouped together?

Answer 1

HSV 1 & 2
VZV
All neurotrophic

Question 2

Which are they lymphotrophic herpes viruses? What disease can all of these viruses cause?

Answer 2

CMV
EBV
HHV 6
Can all cause mono

Question 3

Compare & contrast lympo vs neurotrophic viruses.

Answer 3

BOTH can infect epithelium

Only lympho can infect lymphocytes/other immune cells

Question 4

Name the 4 structural aspects of CMV that you need to know (think inside –> out).

Answer 4

LARGE dsDNA genome
Capsid
Tegument
Envelope

Question 5

What are the 3 categories of CMV genes?

Answer 5

IE - immediate early
E
L

Question 6

IE genes:
Need protein synthesis?
Fxn
Where & when in cell

Answer 6

DON'T need protein synthesis
Gene products fxn in viral DNA synthesis
Detected:
- Nucleus 
- 1st (12-20 hrs post infection)

Question 7

E genes:
Need protein synthesis?
Fxn
Where & when in cell

Answer 7

Need protein synthesis to create gene products
–> fxn in DNA replication + viral protein mod
Detect:
- Cytoplasm
- Nucleus

Question 8

L genes:
Fxn
Where & when in cell

Answer 8

Gene products = structure
Cytoplasm
Nucleus
Last - 48hrs post infection

Question 9

What genetic material is found in CMV’s tegument? What does it code for?

Answer 9

4 mRNAs
Code own IE, E & L genes
Code microRNAs

Question 10

What do microRNAs do?

Answer 10

Control viral & cellular gene expression

Question 11

What are the 3 types of infection timeframes that CMV can have?

Answer 11

Permissive = lytic infection
Latent
Persistent

Question 12

Which tissue & cell type is permissive CMV found in?

Answer 12

Epithelial cells

Macrophages

Question 13

Which cells is latent CMV in?

Answer 13

Hemopoietic cells (in bone marrow & liver)

Question 14

Which cells is persistent CMV in?

Answer 14

Lymphocytes
Endothelial cells
Bone marrow stroma

Question 15

Which pt populations are you concerned about for CMV?

Answer 15

Babies - common cause infectious birth defects

IC pts - 1ary or 2ary infection

Question 16

If compromised, lacking which form of immunity is most likely to cause CMV activation/infection?

Answer 16

CD8

Aka CD8 is most important for keeping CMV from reactivating

Question 17

Why do you think about CMV in transplant pts?

Answer 17

CMV+ recipient could receive another strain from the donor

Recipient IC - can’t fight off new strain

Question 18

How can CMV be transmitted?

Answer 18

Most impt:

• Blood transfusions (if right CMV filter not applied)
• Bone marrow or solid organ transplant

Question 19

Which transplant is the exception to CMV concerns?

Answer 19

Bone marrow - replacing entire immune system including previous immunity!

Question 20

Most common CMV presentation?

Answer 20

Asymptomatic

Question 21

CMV diseases in normal pts

Answer 21

Mono - won’t agglutinate
Idiopathic thrombocytopenic purpura
Hemolytic anemia
Hepatitis

Question 22

CMV diseases in IC pts

Answer 22

MOST ORGAN SYSTEMS
Retinitis
Hepatitis
Gasteroenteritis 
Colitis
Pna
Glomerulopathy
Disseminated disease

Question 23

Describe CMV pna CXR

Answer 23

“Polar bear in snow storm”

Question 24

What cells will you see in CMV biopsy?

Answer 24

Owl’s Eye Cell - BIG epi cells

• Lungs
• GI (colitis)
• Kidneys

Question 25

What is a distinctive characteristic of CMV in lesions?

Answer 25

Hemorrhage

Question 26

Describe CMV retinitis

Answer 26

1. Micro-infarcts = white dots (not specific to CMV) | 2. Progress to hemorrhagic ("ketchup on scrambled eggs")

Question 27

What brain/neural pathology might you see in CMV infection?

Answer 27

Periventriculitis = inflammation around ventricles in brain - Also seen in HHV 6 Transverse myelitis/peripheral neuropathy Hearing lose = CN8 involvment

Question 28

Which CMV disease is specific to babies? Symptoms.

Answer 28

Cytomegalic inclusion disease of the newborn - Microephaly - Mental retardation

Question 29

What is the immune response to CMV?

Answer 29

Abs & cell mediated (CD4, 8, NK)

Question 30

Diagnose CMV

Answer 30

``` = measure replication levels 1. PCR 2. Histopath/immunocytochem Other - Shell vial = rapid culture ```

Question 31

What does Shell Vial rapid culture measure?

Answer 31

Abs vs IE & E antigens

Question 32

How do you filter CMV out of blood?

Answer 32

Exclude cells w/ buffy coat

Question 33

Drugs for CMV prophylaxis

Answer 33

Ganciclovir Valgan (Acyclovir)

Question 34

Antiviral to treat CMV

Answer 34

``` Ganciclovir vs Foscarnet - Use the other if resistent Valgan (retinitis) Cidofovir (retinitis only) Hyperimmune globulin - in combos ```

Question 35

Ganciclovir tox

Answer 35

Bone marrow

Question 36

Foscarnet tox

Answer 36

Renal (not if Cr

Question 37

How do you get ganciclovir (& valgan) resistance?

Answer 37

1. (most likely) UL 97 mutation = CMV kinase | 2. UL 54 mutation = DNA pol