CMV, EBV, KSHV

Question 1

CMV, EBV, and human herpesvirus-8 or KSHV all fall into what category?

Answer 1

Human herpesviruses

Question 2

What is the general structure of a herpesvirus?

Answer 2

Icosahedral capsid surrounded by a lipid envelope that contains about a dozen virus-encoded glycoproteins

Question 3

What’s the genome of a herpesvirus like?

Answer 3

Large, linear, double stranded DNA (150-250 kbp)

Question 4

Herpesvirus genomes are replicated in the (cytoplasm/nucleus).

Answer 4

Nucleus

Question 5

Herpes viruses produce _________ in which the primary infection is often asymptomatic. But _________ can occur especially in immune-compromised hosts.

Answer 5

Self-limiting infections; life-threatening infections or cancers

Question 6

What type of replication do herpesviruses undergo?

Answer 6

Lytic

Question 7

Following virus attachment, penetration occurs by _________.

Answer 7

Virus glycoprotein-mediated fusion of envelope and plasma membrane

Question 8

Herpesvirus penetration occurs by a (pH dependent/pH independent) event.

Answer 8

pH independent event

Question 9

What happens after the released nucleocapsid gets in the cell?

Answer 9

1. Migrates to nuclear envelope via microtubules
2. Uncoats
3. DNA enters the nucleus
4. Virion components shut off host macromolecular synthesis

Question 10

What are the parts of the cascade regulation of viral genes?

Answer 10

1. Immediate early (IE) gene expression
2. Early gene expression
3. Late gene expression
4. Virus assembly
5. Virus particle release

Question 11

What are immediate early genes?

Answer 11

Virus-specific transcription factors that use host RNA pol II and stimulate transcription at virus early promotors

Question 12

What are early genes?

Answer 12

Genes that encode many nonstructural proteins and enzymes and use viral DNA pol and thymidine kinase

Question 13

What are late genes?

Answer 13

Genes that encode structural proteins and are dependent on IE TFs plus genome replication for expression.

Question 14

Viral glycoproteins can be transported to the infected cell surface where they cause _______.

Answer 14

Syncytia formation

Question 15

Where in the cell does virus assembly occur?

Answer 15

In the nucleus where nucleocapsids bud first into the perinuclear space

Question 16

T or F: All herpesviruses undergo latency.

Answer 16

T: entire genomes are maintained extrachromosomally in the host indefinitely, but no viruses are produced

Question 17

What are the three stages of latency?

Answer 17

1. Establishment
2. Maintenance
3. Reactivation

Question 18

When does reactivation generally occur?

Answer 18

When there’s a lapse in immunity

Question 19

Reactivation results in ______ and ______.

Answer 19

Production of virus particles and recurrent infection

Question 20

T or F: Anyone infected with a herpesvirus is in the club fo life.

Answer 20

True dat (risk of recurrent infections or other sequelae)

Question 21

What is acyclovir?

Answer 21

An antiviral prodrug that prevents chain elongation from continuing on an actively replicating virus

Question 22

What are the alphaherpesvirinae (3)?

Answer 22

1. HSV-1
2. HSV-2
3. VZV

Question 23

The alphaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.

Answer 23

Neurotropic, aggressive

Question 24

The betaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.

Answer 24

Lymphotropic, insidious

Question 25

What are the betaherpesvirinae? (3)

Answer 25

1. CMV 2. HHV-6 3. HHV-7

Question 26

What are the gammaherpesvirinae? (2)

Answer 26

1. EBV | 2. HHV-8

Question 27

The gammaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.

Answer 27

Lymphotropic, insidious

Question 28

T or F: CMV is highly contagious.

Answer 28

F

Question 29

CMV is more prevalent in (lower/higher) socioeconomic classes.

Answer 29

Lower (80% of adults in lower class, 50% of adults in higher class)

Question 30

What are the general steps of the lytic cycle? (6)

Answer 30

1. Virus attachment 2. Penetration 3. Uncoating 4. Programmed expression of viral genes 5. Assembly 6. Release

Question 31

Where is CMV found?

Answer 31

Saliva, urine, breastmilk, semen, cervical secretions, blood

Question 32

Who's the most at risk for CMV?

Answer 32

Neonates, day care workers, pregnant workers, immunocompromised patients, gay men

Question 33

Neonatal CMV infections can result in ________.

Answer 33

Retardation and deafness

Question 34

CMV infection occurs through _________.

Answer 34

Direct contact with secretions (not by aerosol)

Question 35

Where is primary CMV replication taking place? Secondary?

Answer 35

Primary in epithelial cells followed by spread to lymphoid tissue

Question 36

What do CMV-infected cells look like?

Answer 36

Large, puffed up

Question 37

T or F: Most CMV infections in neonates and adults are asymptomatic.

Answer 37

T

Question 38

Most _________ get CMV infection with pnemonitis.

Answer 38

Organ transplant patients. Don't forget this!

Question 39

AIDS patients are prone to CMV _____, _____, and ______.

Answer 39

Retinitis, colitis, pneumonitis

Question 40

How can you diagnose CMV?

Answer 40

ELISA, PCR, Shell vial assay (indirect immunofluorescent used to detect an immediate early protein after 24 hours of cell culture infection)

Question 41

What can you use to limit complications of CMV in transplant patients?

Answer 41

CMV Ig and ganciclovir

Question 42

What is ganciclovir?

Answer 42

Guanosine analog that requires phosphorylation by viral kinase for activity -Triphosphate form inhibitys CMV polymerase

Question 43

What is the downside of the triphosphate form of ganciclovir?

Answer 43

It is more toxic to the host than acyclovir

Question 44

Side effects of ganciclovir

Answer 44

Neutropenia and GI bleeding

Question 45

_______ are approved for CMV retinitis treatment in AIDS patients.

Answer 45

Gancyclovir, Cidofovir, Foscarnet

Question 46

What is foscarnet?

Answer 46

A pyrophosphate analog that inhibits DNA polymerase but doesn't require phosphorylation for activity

Question 47

What is cidofovir?

Answer 47

A competitive inhibitor of CMV DNA pol that does not require viral kinase action for activity (like ganciclovir does)

Question 48

Who typically gets EBV infection at an early age?

Answer 48

People in a low socioeconomic setting

Question 49

EBV can lead to what common disease?

Answer 49

Infectious mononucleosis

Question 50

_____% of the adult population contains Ab to EBV.

Answer 50

95%

Question 51

EBV can cause ________ in immunocompromised hosts.

Answer 51

Oral hairy leukoplakia (productive infection of tongue epithelial cells)

Question 52

____________ from EBV is seen in some transplant patients.

Answer 52

Posttransplant lymphoproliferative disease (PTLD)

Question 53

Which cancers is EBV associated with?

Answer 53

Burkitt's lymphoma and nasopharyngeal carcinoma

Question 54

How does EBV spread from person to person?

Answer 54

Through saliva by kissing <3

Question 55

What is EBV's incubation period?

Answer 55

4-7 weeks

Question 56

Initial replication of EBV occurs in _______, then spreads to _______.

Answer 56

Initial replication in oropharyngeal epithelium --> lymphocytes --> liver and spleen

Question 57

Where does EBV remain latent?

Answer 57

Throat epithelium and B cells

Question 58

T or F: Oral shedding of EBV occurs for many months.

Answer 58

F: occurs for many weeks

Question 59

T or F: Most EBV infections are asymptomatic.

Answer 59

T

Question 60

What are the symptoms of infectious mononucleosis?

Answer 60

Sore throat, fever, malaise, lymphadenopathy

Question 61

How can you diagnose EBV?

Answer 61

Symptoms and presence of at least 50% atypical large lymphocytes with lobulated nuclei

Question 62

What is EBNA and what does it indicate?

Answer 62

An EBV antigenic marker - EBNA 1 maintains genome replication in dividing B cells - Conversion to anti-EBNA IgG indicates resolution of primary infection

Question 63

Where will you find VCA?

Answer 63

It's a viral capsid antigen on EBV

Question 64

Anti-VCA IgM indicates _______.

Answer 64

Primary infection

Question 65

Anti-VCA IgG without ________ indicates primary infection.

Answer 65

anti-EBNA

Question 66

Anti-VCA IgGa with anti-EBNA indicates ______.

Answer 66

Past infection

Question 67

Where will you detect EA (early antigen)?

Answer 67

In cells that do not produce virus

Question 68

What does the monospot test look at?

Answer 68

Heterophile antibodies that agglutinate sheep RBCs (distinguishes EBV mono from CMV mono)

Question 69

How do you treat oral leukoplakia?

Answer 69

Acyclovir

Question 70

How do you treat PTLD?

Answer 70

Stop immunosuppression and monitor for rejection

Question 71

What is PTLD?

Answer 71

Uncontrolled proliferation of B cells due to their transformation of EBV and no CTLs to control them

Question 72

Where is Burkitt's lymphoma endemic?

Answer 72

Central Africa and New Guinea

Question 73

What three factors is Burkitt's lymphoma associated with?

Answer 73

1. Early EBV infection --> latency 2. C-MYC activation 3. Malaria

Question 74

T or F: Association of nasopharyngeal carcinoma with EBV is worldwide.

Answer 74

T

Question 75

Where does nasopharyngeal carcinoma have the highest frequency and what's a possible reason for this?

Answer 75

Southern China -- dat high salt diet

Question 76

How does nasopharyngeal carcinoma present?

Answer 76

Painless lump in the neck

Question 77

T or F: HHV-8 is necessary and sufficient to cause Kaposi's sarcoma (KS) ?

Answer 77

F: Necessary but not sufficient

Question 78

Human herpes virus 8 is aka ______.

Answer 78

KSHV

Question 79

Where do KS tumors occur?

Answer 79

In the lining of the lymphatic system (fill lymphatic channels with blood cells --> bluish, bruised lesions)

Question 80

Where is KS prevalent?

Answer 80

Mediterranean and sub-Saharan Africa (not sexually transmitted in these populations)

Question 81

In the US, who are most of the KS patients? How is it transmitted?

Answer 81

AIDS patients, Sexually transmitted/via saliva (not present in semen and vaginal secretions)

Question 82

Whats the typical incubation period for KS?

Answer 82

10 years

Question 83

T or F: When symptomatic for KS, treatment in AIDS patients targets the tumor or HIV but not HHV-8.

Answer 83

T

Question 84

Other than KS, what B cell abnormalities does HHV-8 cause?

Answer 84

1. Primary effusion lymphoma | 2. Castleman's disease

Question 85

What is primary effusion lymphoma?

Answer 85

KSHV+ NHL commonly found in body cavities (mean survival 2-6 months)

Question 86

What is Castleman's disease?

Answer 86

Lymph node tumors that are KSHV+ (not strictly cancer)