Exam #7: Viral Infections of the Circulatory, RES, & Lymphatic System

Question 1

List the characteristics of EBV.

Answer 1

• Herpesvirus (lytic & latent phases)
• Enveloped
• dsDNA

Question 2

List the diseases that are associated with EBV. What patient populations are most likely to develop the different diseases associated with EBV?

Answer 2

• Mononucelosis– adolescents & adults
• Oral Hairy Leukoplakia–Immunocompromised
• Burkitt’s Lymphoma–children in central Africa
• Hodgkin’s Disease–Multiple populations
• Nasopharyngeal Carcinoma–Southeast Asia & China
• PTLD–Transplant patients

Question 3

What diseases associated with EBV are caused by the productive phase?

Answer 3

Mononucleosis

Oral Hairy Leukoplakia

Question 4

What diseases associated with EBV are associated with the latent phase?

Answer 4

Burkitt’s Lymphoma
Hodgkin’s Disease
Nasopharyngeal Carcinoma
PTLD

Question 5

What does EBV use for attachment & entry?

Answer 5

The receptor for the C3d component of compliment, which is found on a limited number of cells, including B-cells & epithelial cells of the oro & nasopharynx

Question 6

Where does EBV replicate?

Answer 6

• Initially, EBV replicates with oral epithelial cells & causes lysis
• After lysis of epithelial cells, EBV infects B-cells

Question 7

How is EBV transmitted?

Answer 7

Saliva

Question 8

Describe the pathology of EBV.

Answer 8

• Initially, EBV replicates with oral epithelial cells & causes lysis
• After lysis of epithelial cells, EBV infects B-cells
• B-cell infection causes B-cells to differentiate into lymphoblasts
• Lymphoblasts proliferation leads to high levels of antibodies that bind antigens other than EBV, called heterophile antibodies
• In the first few days of infection, a robust cytotoxic T-cell immune response targets & kills EBV-infected immune cells, which leads to the symptoms of mononucleosis
• Some EBV-infected B-cells evade cytotoxic T-cells & become memory B-cells that can be reactivated

Question 9

What are the symptoms of EBV reactivation?

Answer 9

In healthy individuals, none–asymptomatic

Question 10

What EBV genes are associated with carcinogenesis?

Answer 10

1) Latent Membrane Protein 1 (LMP1)= CD40 homologue that is constitutively active & results in increased growth & suppressed apoptosis
2) Latent Membrane Protein 2 (LMP2)= increased growth of B-cells
3) EBNA1= inhibits apoptosis

Question 11

When are EBV primary infections most common worldwide, & in the US?

Answer 11

World= <5 
US= teens

Question 12

What are the symptoms of mononucleosis?

Answer 12

Fever 
Malaise 
Exudative pharyngitis 
Splenomegaly 
Tender lymphadenitis

Question 13

What biochemical marker is diagnostic for mononucleosis?

Answer 13

Heterophile antibodies

Question 14

What complication is associated with mononucleosis?

Answer 14

Splenic rupture; thus, patients with mononucleosis are in instructed to refrain from physical exertion

Question 15

What causes the symptoms of mononucleosis?

Answer 15

Cytotoxic T-cell response to EBV infected B-cells

Question 16

What can happen when a patient with mononucleosis is given ampicillin?

Answer 16

Rash

Question 17

How long is the typical incubation period in mononucleosis?

Answer 17

2 month incubation period

Question 18

When are heterophile antibodies detected in mononucleosis?

Answer 18

A few days into symptomatic infection

Question 19

What antibodies are associated with early EBV infection?

Answer 19

Anti-EA (Early Antigen)

Anti-VCA, IgM (Viral Capsid Antigen)

Question 20

What antibodies are associated with late EBV infection?

Answer 20

Anti-EBNA (Epstein Barr Nuclear Antigen)

Anti-VCA, IgG

Question 21

How is mononucleosis diagnosed?

Answer 21

• Mono spot test= heterophile antibody agglutination of sheep or horse RBCs
• Antibodies to EBV–mainly IgM to viral capsid antigen (VCA)

Question 22

What are Downey cells?

Answer 22

Large atypical T-cells that have an indented cell margin are a classic feature of EBV infection

Question 23

How is there a vaccine for mononucleosis?

Answer 23

No

Question 24

How is mononucleosis treated?

Answer 24

• Rest & hydration
• Avoidance of strenuous activity

*Don’t want splenic rupture

Question 25

What effect do antiviral drugs have on EBV infection?

Answer 25

None really--symptoms are due to the immune response to the virus, NOT the virus itself *Acyclovir will inhibit the viral polymerase, but it does not have an impact on the clinical course of the disease

Question 26

What is Oral Hairy Leukoplakia?

Answer 26

Wart-like pattern on lateral surface of the tongue | - Seen in patients with immuosuppresion (~300 CD4+ T-cells)

Question 27

How is Oral Hairy Leukoplakia treated?

Answer 27

- Antiherpetic drugs (acyclovir) | - Podophyllin resin

Question 28

What is Burkitt's Lymphoma?

Answer 28

B-cell tumor often presenting in the jaw of children

Question 29

What genetic mutations are associated with Burkitt's Lymphoma?

Answer 29

- Translocation (8 x 14) of the c-myc oncogene being put under the control of a very active promoter e.g. immunoglobulin genes - Leads to high levels of c-myc activity & a high proliferative index *This is the most rapidly progressing human tumor

Question 30

How is Burkitt's Lymphoma treated?

Answer 30

Chemotherapy, which has a 70-80% cure rate in children and young adults

Question 31

What co-factors are associated with Burkitt's Lymphoma?

Answer 31

Immunosuppression is highly associated with Burkitt's Lymphoma, which is partly why there is a high incidence in areas where chronic malaria is endemic (central Africa)

Question 32

What is Hodgkin's Disease?

Answer 32

B-cell cancer that is NOT associated with any specific translocations vs. Burkitt's lymphoma

Question 33

What is the typical presentation of Hodgkin's Disease?

Answer 33

- Nontender, palpable lymphadenopathy in neck, supraclavicular, or axilla - Mediastinal adenopathy - Fever, night sweats, & weight loss

Question 34

What is the hallmark of Hodgkin's Disease?

Answer 34

- Reed-Sternberg cell | - A large cell with two or more nuclei or nuclear lobes, each of which contains an eosinophilic nucleolus

Question 35

How is Hodgkin's Disease treated?

Answer 35

Radiotherapy Chemotherapy *Not that localized Hodgkin's Disease is cured in >90% of patients

Question 36

What is nasopharyngeal carcinoma?

Answer 36

Epithelial cancer that originates in the nasopharynx

Question 37

Where is nasopharyngeal carcinoma prevalent?

Answer 37

SE Asia | Africa

Question 38

What are the symptoms of nasopharyngeal carcinoma?

Answer 38

- Facial pain - Feeling of fullness in the sinus or throat - Hearing loss

Question 39

How is nasopharyngeal carcinoma treated?

Answer 39

Radiotherapy | Chemotherapy

Question 40

What is PTLD?

Answer 40

Post-transplantation Lymphoproliferative Disorder | - abnormal proliferation of lymphoid cells in a transplant patient

Question 41

What are the symptoms of PTLD?

Answer 41

Fever Fatigue Weight loss Progressive encephalopathy

Question 42

What is the major risk factor for PTLD?

Answer 42

EBV at the time of transplant

Question 43

How is PTLD diagnosed?

Answer 43

- Histological analysis of tissue | - Detection of EBV genomes by in situ hybridization

Question 44

How is PTLD treated?

Answer 44

1st line= Reduce immunsuppression 2nd= Rituximab (anti-CD20 ab) 3rd= Conventional chemotherapy

Question 45

List the characteristics of CMV.

Answer 45

Herpesvirus Enveloped dsDNA

Question 46

What diseases can be caused by CMV? How are these disease states dependent on the immune status of the host?

Answer 46

- Normal individuals = Mononuceolsis-like disease - Babies of seronegative mothers= Cytomogalic inclusion disease - AIDS & severely immunosuppressed= Multisite symptomatic disease

Question 47

How is CMV transmitted?

Answer 47

Bodily fluids - Saliva - Breast milk - Urine - Fomites - Sex

Question 48

How is CMV diagnosed?

Answer 48

Detection of viral DNA or virus culture from diseased tissue

Question 49

How is CMV treated?

Answer 49

1st Line: - Gancycloir= converted to viral polymerase inhibitor by CMV enzymes - Valganciclovir= converted to gangyclovir in the body that has an increased bioavaliablity 2nd Line: - Cidofovir= converted to viral polymerase inhibitor by cellular enzymes, but MORE TOXIC than gancyclovir - Foscarnet= direct inhibitor of the CMV polymerase, but associated with renal toxicity

Question 50

What toxicity is associated with Gancyclvir?

Answer 50

Bone marrow toxicity & drug-related neutropenia

Question 51

What is CMV Infectious Mononucleosis-Like Illness?

Answer 51

CMV infection of immunocompetent school-aged children & adults that results in mononucleosis-like disease

Question 52

What are the symptoms of CMV Infectious Mononucleosis-Like Illness? How can you tell the difference between CMV & EBV?

Answer 52

Fever Fatigue Pharyngitis Downey Cells * No heterophile antibody production in CMV * *Exudative pharyngitis & cervical lymphadenopathy are rare in CMV

Question 53

What is Cytomegalic Inclusion Body Disease?

Answer 53

Disease of the newborn that is primarily seen in children born to mothers that suffered primary CMV infection in utero.

Question 54

What symptoms are associated with Cytomegalic Inclusion Body Disease?

Answer 54

Hepatosplenomgealy Jaundice Petechaie/ Rash And, - Microcephaly - Growth retardation

Question 55

How is Cytomegalic Inclusion Body Disease prevented?

Answer 55

Interrupt CMV transmission in body fluids by: - Handwashing - Avoid sharing drinks & toothbrushes with young children - Avoid contact with saliva when kissing a young child Maternal treatment with CMV immunoglobulin during pregnancy

Question 56

What is the most common viral pathogen complicating organ transplant?

Answer 56

CMV

Question 57

What is the CD4 T-cell count of an AIDS patient presenting with CMV related disease?

Answer 57

Between 50 & 100

Question 58

What diseases are caused by CMV that are seen in transplant recipients?

Answer 58

- CMV pneumonitis - Ulceration of the GI Tract - Increased risk of Graft vs. Host Disease

Question 59

What diseases are caused by CMV in AIDS patients?

Answer 59

CMV Retinitis

Question 60

How is CMV infection prevented in transplant recipients?

Answer 60

Donor matching Prophylaxis CMV Ig

Question 61

How is CMV prevented in AIDS patients?

Answer 61

Maintenance therapy with antivirals when reaching threshold levels of CD4+ T-cells

Question 62

How is CMV treated?

Answer 62

IV antivirals