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43 Cards in this Set

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What subfamily does EBV belong to?
Gammaherpesvirinae
Gamma herpes viruses are characterized by:

- infection
- cell target
Latent

B-cells (proliferation)
HHV-4 is also known as?
Epstein Barr Virus
HHV-8 is also known as?
Kaposi's Sarcoma Herpes Virus
T/F - EBV is the most prevalent of human virues.
True
EBV transmission. Describe
Typical direct, close personal contact
- saliva
- blood
- tissue transplant
- sexual
EBV:

- genome type
- linear or circular
- capsule
- envelope
- unique structure
dsDNA

Linear (becomes circular in cell)

Icosohedral

envelope

tegument
EBV will INITIALLY infects what cells?

EBV eventually ENDS UP infecting what cells?

Expansion of viral genome done through what?

How long does it stay in host?
Oropharyngeal epithelium

B-cells

Forced proliferation of B-lymphocytes

Lifetime
List two benign diseases of EBV and describe their association with patients.
Infectious Mononucleosis (IM)
- targets immunocompetent

Oral Hairy Leukoplakia (OHL)
- targets immunosuppressed
What is the classic triad for EBV induced IM?
Fever

Sore throat (pharyngitis)

Cervical lymphadenopathy
What is the hematological finding associated with EBV induced IM?
Greater than 10% ATYPICAL lymphocytes
What is the serotological finding associated with EBV induced IM?
Transient HETEROPHILE antibodies

Permanent EBV-sprecific antibodies
When EBV infects a resting B-cell, describe the receptor interactions for:

- binding
- fusion/entry
B-cells CD21 receptor binds to viral gp350

B-cell HLA class II (HLA-DR) coreceptor binds to viral gp42-gL-gH
When progeny viruses leave the resting B-cell, why do they lack a gp42?

What is the consequence of this?
The gp42 will bind with the internally synthesized cellular HLA-DR. This causes them to become degraded along the proteolytic pathway.

Thus only gL-gH is found on the progeny virus.

This is beneficial b/c epithelial cells will not allow entry to viruses with gp42, but will allow gL-gH entry.

EBV can then make new progeny with gL-gH AND gp42 b/c epithelial cells do not have HLA molecules for it to bind to.
EBV replication:

- rate
- requires what? why?
- depends on what enzymes
Once per cell cycle

EBNA-1 b/c it binds to EBV origin of replication

Cellular enzymes
Why would acyclovir not work on EBV induced IM?

Can acyclovir be used at all when dealing with EBV diseases?
Because this is a disease of latency and is dependent on cellular enzymes.

ACV is used to target viral polymerase and to inhibit lytic viral diseases

Yes, can use with Oral Hairy Leukoplakia.
EBV-Specific Cytotoxic T-cells:

- infected with EBV?
- targets what
- eliminates what
Non-infected

EBV latency proteins (EBNAs & LMPs)

proliferatint B cells
T/F - Heterophile antibodies react with EBV antigens.
False.

These Ab target the massive random antibodies created by the proliferating B-cells.
What test will detect heterophile antibodies?

How does this test work?
Monospot test

These antibodies are IgM class that agglutinate sheep RBC's.
EBV-specific antibodies:

- persist for how long?
- useful for what kind of infection?
- essential for diagnosis?
For LIFE

Acute

Rarely, but can be used to distinguish for leukemia
Question
Answers
What is the average incubation period for IM?
50-60 days
What organ complication can occur with the overload of B-cells in IM?
Splenic rupture.
What are the hematological complications of IM?
Hemolytic anemia
Thrombocytopenia
Neutropenia
What is the most frequent cause of death in IM complications?

What is the recovery prognosis for such a complication?
Encephalitis/Meningitis

85% complete recovery
IM usually manifests how for children:

- usually what symptoms during seroconversion?
- any atypical presentations?
Usually asymptomatic seroconversion

Neutropenia
Periorbital swelling
Rash
Respiratory infection
What is so unique about the serology of IM children?
50% - HETROPHILE NEGATIVE !!!!

(80% when less than 4 y.o.)
IM manifestion for young adults:

- symptomatic association
- serology
50% symptomatic at primary infection

90% heterophile positive
IM manifestation for elderly:

- common symptoms x3
Fever
Abdominal pain
Hepatic abnormalities
T/F - For IM, is acyclovir used?

why or why not?
Not indicated

It inhibits EBV replication, yet IM is a disease associated EBV LATENCY!
What is the best treatment for IM?
Supportive
When would you use corticosteroids for IM? x3
Impending airway obstruction

Severe thrombocytopenia

Hemolytic anemia
List all the EBV associated disease that involve B-cells.
Burkitt's Lymphoma

Hodgkin's Lymphoma
IM
PLTD (post transplant lymphoproliferative disorder)
Describe the genetic association with Burkitt's Lymphoma.
Associated with a translocation involving chromosome 8 (c-myc gene)

AND

chr 2, 22, 14
EBV Latency proteins

- how many LMPs (latent membrane proteins)

- how many EBNAs (Epstein Barr Nuclear Antigens)
3

6
EBV latency proteins are:

- critical for what in vivo
- required for what in vitro
B-cell proliferation

Cell transformation
What is unique about the total CD8+ T-cell pool in association with EBV?
EBV-specific CD8+ T-cells constitute 5%
Specify the EBV latency proteins in the tumor tissues associated with the following:

- Post transplant lymphomas
- Nasopharyngeal Carcinoma (NPC)
- Gastric Carcinoma
- Hodgkin's Lymphoma
- Burkitt's Lymphoma
All 9

EBNA-1, LMP-1, LMP-2
EBNA-1, LMP-1, LMP-2
EBNA-1, LMP-1, LMP-2

Only EBNA-1
In order to survive T-cell detection, EBV will do what?
Downregulate latency proteins to just EBNA-1, LMP-1, and LMP-2
Describe the latency proteins associated with exploiting the physiological B-cell pathway.
EBNA-1 : maintains episome in cell

LMP-1 : Mimicry of CD40 receptor

LMP-2 : Mimicry of B-cell receptor/surface immunoglobulin
List the EBV associated disease that involves epithelial cells. x3
Nasopharyngeal carcinoma (NPC)

Oral Hariy Leukopenia (OHL)

Gastric Carcinoma
Nasopharyngeal Carcinoma (NPC)

- prevalent population
- characterized by what type of infection
- symptom
Southern Asia + Alaskan eskimos

Latency

Highly metastatic beginning in the OROPHARYNX, and may travel to cervical.
Oral Hairy Leukoplakia (OHL)

- prevalent population
- characterized by what type of infection
- Symptom
- Can look like what other syndrome?
Immunosuppressed patients (AIDS)

Active Viral Replication

Benign hyperplastic lesion of epithelial cells in tongue

Candida