Viruses of Hematopoietic System

Question 1

Virus

Answer 1

Particles that can transmit genetic information from one cell to another, and from one organism to another

Question 2

Why is a virus not really an organism?

Answer 2

It requires proteins that are made by the host cell.

–But it encodes it’s own proteins.

Question 3

Viral Replication Requires?

Answer 3

1. Gaining entry to host cell
2. Replicating proteins
3. Replicating nucleic acids
4. Packaging proteins & nuclei acids into virions
5. Exiting the cell.

Question 4

Antiviral Therapy

Answer 4

-Inhibit viral genome replication by mimicking the shape of a nucleotide and ‘plug up’ the enzymes that replicate the viral genome

Question 5

Requirement of antiviral therapies?

Answer 5

Drugs must have higher affinity for the viral enzyme than for the host enzyme.

Question 6

Acycloivir

Answer 6

• Nucleoside analog

- viral thymidine kinase needed to phosphorylate prodrug –> active drug

Question 7

Thymidine Kinase expressed when?

Answer 7

During S phase
aka virus can only replicate in proliferating cells.
BUT WAIT– virus has it’s own TK enzyme (classic is HSV)
–Cool, now we can make drugs that just disrupt viral TK :)

Question 8

Viral Pathogeneisis:
Acute
Long term

Answer 8

Acute: cell death & inflammation

Long term: malignancies & immune suppression→opportunistic infections

Question 9

Viruses oncogenes cause cancer in different spots:

Answer 9

1. G1→ S phase checkpoint
2. Regulation of cell death by apoptosis
3. Immunological synapse (normal T cell activation)

Question 10

Regulation of cell death by apoptosis

Answer 10

Bid/Bax complex=apoptotic (cytochrome C released into cytoplasm)

Bcl-2/Bid complex=antiapoptotic (doesn’t let cytochrome C release)

Question 11

Regulation of cell death by apoptosis

Answer 11

Bid/Bax complex=apoptotic (cytochrome C released into cytoplasm)

Bcl-2/Bid complex=antiapoptotic (doesn’t let cytochrome C release)
–high ratio–>more likely to become malignant.

Question 12

Cancer at Immunological Synapse:

Answer 12

Normal: T cell activated –> B cell proliferates –>secretes specific antibody

Epstein-Barr Virus= expresses homologs of host proteins that regulate B cell expansion–> Lymphoma :(

Question 13

What components to viruses always have?

Answer 13

Protein and nucleic acid

Some have lipid envelope that is embedded with glycoproteins

Question 14

Tropism?

Answer 14

What organism do they infect?

What cell types do they infect?

Question 15

Role of thymidine kinase?

Answer 15

Regulate GTP production

Question 16

-dsRNA, segmented
NO envelope (tick is vector!)
Icosahedral 
Tropism: pro-erythroblasts --> mature RBCs
Saddleback fever pattern

Answer 16

Colorado Tick Fever Virus

Question 17

Colorado Tick Fever Virus

Symptoms and tx

Answer 17

Saddleback fever pattern
-travel to mountains in West

Tx: supportive

Question 18

Cytomegalovirus (CMV, HHV5)
Tropism:
Symptoms:
Tx:

Answer 18

Herpes virus (dsDNA, enveloped, icosahedral)

Tropism: Systemic. LATENT in CD34+ cells (monocyte–>macrophage)

Symptoms:

• – CMV infectious mononucleosis: Heterophile Ab negative, OWL’S EYES CELLS
• –congenital systemic CMV=deafness

Tx: supportive. Ganciclovir for immunocompromised pts

Question 19

Herpes viruses characteristics

Answer 19

dsDNA
Enveloped
Icosahedral

CMV, HHV6&7, EVB, Kaposi sarcoma (HHV8)

Question 20

Only non enveloped viruses

Answer 20

Colorado Tick Fever Virus

Parvovirus B19

Question 21

HHV-6 & HHV-7 :exanthem subitum
Tropism:
Symptoms:
Tx:

Answer 21

–> ROSEOLA
Tropism: CD4+ T cells, (PBMNCs, epithelial)
Symptoms: rash after fever resolves
heterophile Ab negative mononucleosis

Tx: Supportive (anciclovir for immunocompromised pts)

Question 22

HHV-6 & HHV-7 :exanthem subitum
Tropism:
Symptoms:
Tx:

Answer 22

–> ROSEOLA
Tropism: CD4+ T cells, (PBMNCs, epithelial)
Symptoms: rash after fever resolves
heterophile Ab negative mononucleosis

Tx: Supportive (anciclovir for immunocompromised pts)

Question 23

Kaposi Sarcoma herpes virus (KSHV, HHV8)

Tropism:
Symptoms:
Tx:

Answer 23

Tropism: epithelial cells, B cells

Symptoms: in immunocompromised pts only: kaposi sarcoma, primary effusion lymphoma, multifocal Castlemans disease

tx: Ganciclovir, cidofir, foscarnet

Question 24

Parvovirus B19

Answer 24

ssDNA
NON ENVELOPED
icosahedral

Tropism: erythroid progenitor cells

symptoms: erythema infectiosum: fiery red RASH on CHEEKS. Transient aplastic crisis with underlying anemia (think of cells it targets)
tx: supportive

Question 25

Only virus with ssDNA?

Answer 25

Parvovirus B19

Question 26

Human T lymphotrophi virus-1

HTLV-1

Answer 26

Retroviridae
ssRNA, positive
enveloped
icosahedral

Tropism: T cells (HTLV-1 mostly CD4+)

symptoms: Acute T cell lymphoma/leukemia (ATL): Viral transcription factor Tax drives proliferation; blocks apoptosis.
HAM/TSP: inflammation on the spine

Tx: chemotherapy/ BMT

Question 27

Retroviridaes?

Answer 27

Human T Lymphotrophi virus 1

HIV

Question 28

Ebola virus

Answer 28

Filoviridae
ssRNA, negative
enveloped
HELICAL/complex

Tropism: Macrophages

Sx: Hemorrhagic fever

Tx: supportive

Question 29

ssRNA viruses

Answer 29

Human T lymphotrophi (ssRNA, positive)

HIV (ssRNA, positive)

Ebola(ssRNA, negative)

Question 30

Viruses you treat:

Answer 30

Kasposi Sarcoma: ganciclovir, cidofir, foscarnet

HTVL-1: chemo/BMT

If immunocompromised, tx CMV and HHV6&7 with ganciclovir.

Question 31

Kaposi’s encodes vCyclin, a protein with homology to human cyclin D, expect what?

Answer 31

increased transcription of E2F regulated genes.

Question 32

Kaposi’s encodes vCyclin, a protein with homology to human cyclin D, expect what?

Answer 32

increased transcription of E2F regulated genes.

Question 33

G1—>S checkpoint: what is going on?

Answer 33

1. Cyclin D/ CDK4 activation
2. Phosphorylates RB
3. RB lets go of E2F
4. E2F goes and makes a bunch of enzymes for cell replication and division.