L36 Herpesvirus

Question 1

Herpesviridae persists in host for life. T/F?

Briefly describe/

Answer 1

T
Primary infection > asymptomatic/symptomatic
> Latent infection (Nervous/Lymphoid)
> Reactivation (symptomatic/asymptomatic)

Question 2

Herpesviridae has oncogenic property. Give 3 examples.

Answer 2

1. Nasopharyngeal carcinoma HHV4 (EBV)
2. Burkitt’s lymphoma HHV4 (EBV)
3. Kaposi’s sarcoma HHV8 (KSV)

Question 3

Herpesviridae can be eliminated by alcohol rub?

Answer 3

Yes, Enveloped virus
- damage by soap and water, alcoholic rub due to lipid capsule

VS
non-enveloped: adenovirus

Question 4

Among 9 types of HHV (Human herpesviruses), which of them are of high prevelance?

Answer 4

All except
HHV2 (Herpes simplex virus type 2) and
HHV 8 Kaposi’s sarcoma-associated herpesvirus (KSHV)

Question 5

Among 9 types of HHV (Human herpesviruses), which of them are dermatotrophic? (tend to infect the skin and cause rashes)

Answer 5

All except
HHV4 (Epstein-Barr virus)
HHV5 Human cytomegalovirus (CMV)

Question 6

Among 9 types of HHV (Human herpesviruses), which of them are with neurolatency?
(use nerves as site of latency)

Answer 6

All except
HHV4 (Epstein-Barr virus),
HHV5 (Human cytomegalovirus,
HHV 8 Kaposi’s sarcoma-associated herpesvirus

Question 7

Among 9 types of HHV (Human herpesviruses), which of them are with lympholatency?
(use lymphs as site of latency)

Answer 7

HHV4-HHV8

// all except 1-3

Question 8

Herpes simplex virus 1 - Primary infection
A. Early childhood >95%
B. Transmitted by kissing - shed virus in saliva
C. Usually asymptomatic
D. Causes gingivostomatitis
E. Causes rash typically

Answer 8

E is wrong
D: in children
- Pharyngitis and tonsilitis in older
- resolves in 2-3 weeks

Question 9

After primary infection in Herpes simplex virus 1, what happens in

1. Latency - reside at?
2. Reactivation - Trigger? Causes? Complication?

Answer 9

1. Latency - reside at
   - local sensory dorsal root ganglion
   - trigeminal ganglia, brain
2. Reactivation
   - Trigger: Stress, UV light, injury to innervated tissue, immunosuppression and non-specific triggers
   - 40-50% had herpes labialis

• Cx: Herpes simplex encephalitis (actively damage brain)

Question 10

Mode of transmission of Herpes simplex 2 virus?
What are the typical symptoms? (5)
Complications? (2)

Answer 10

Sexually transmitted
- more severe than oral infection

S/S

• Fever, dysuria, pain (vesicular lesions at genitalia area)
• Perianal, proctitis

Cx

• aseptic meningitis
• radiculomyelitis

Question 11

After primary infection in Herpes simplex virus 2, what happens in

1. Latency - reside at?
2. Reactivation - compared to primary infection?

Answer 11

1. Latency - reside at
   - local sensory dorsal root ganglion
   - sacral ganglia
2. more frequent than oral infection (vesicular lesions at genitalia area);
   but fever vesicles, less painful than primary infection

Question 12

Cause of neonatal herpes?

Answer 12

Primary HSV-2 infection or reactivation at mother > vaginal delivery

Question 13

What is the name for HHV-3?

What infection does it cause?

Answer 13

Varicella zoster virus

- Chicken pox

Question 14

Mode of transmission of Varicella zoster virus (HHV-3)?

Answer 14

Airborne

- only this and measles are imp airborne viruses

Question 15

What is the clinical course of VZV primary infection? (3)

Answer 15

Chickenpox

1. Vesicular rash starts on face > trunk > limbs (Central to peripheral)
2. Pus due to bacterial infection
3. More complications in adults, e.g. pneumonia, encephalitis

• subside after 1 week

Question 16

For Varicella Zoster virus, there is life-long latency in ______________ (site where it resides)?

What happens in reactivation Zoster?
- Chance of reactivation increases sharply after >60 years old

Answer 16

Posterior root ganglia (trigeminal, thoracic)

Reactivation zoster = Shingles

• affects area of nerve supply
• pain/ numbness before rash
• severe pain may persist after healing (post-herpetic neuralgia)

Question 17

Where are the common sites for VZV reactivation - shingles/zoster (3)?

Answer 17

1. Thoracic and lumbar T5-L2
2. Trigeminal nerve (ophthalmic branch)
3. Ramsay-Hunt syndrome: facial nerve palsy, geniculate ganglion VII nerve

Question 18

How can we prevent Varicella Zoster Virus infection?

Answer 18

1. Vacccine
   - Live-attenuated vaccine, alone or combined with MMR
   - Zoster: prevent reactivation by
   > Live-attenuated/ recombinant subunit
   > recommended for >50/60 years old
2. Immunoglobulin (HNIG, VZIG)
   - post-exposure prophylaxis for high risk patients:
   a) susceptive pregnant women/
   b) immunocompromised/
   c) neonate

Question 19

Which of the following are correct regarding the diagnosis for HSV and VZV?
A. Typical clinical presentation thus seldom requires lab investigations
B. Viral nucleic acid detection by PCR is used in CSF
C. Viral antigen detection by immunofluoresence is used
D. A good skin scrap sample is collected for IF
E. Serology is not useful due to cross-reaction between HSV and VZV

Answer 19

All of the above

EM is not used too

Question 20

Name for HHV-4?

Answer 20

Epstein-Barr virus

Question 21

Epstein-Barr virus
A. Common in young children, transmitted via saliva and genital secretions
B. Mostly asymptomatic
C. Infectious mononucleosis - fever, enlarged cervical LN is a complication
D. Primary infection can be in teenagers
E. Persistence and latency has frequent shedding at feces

Answer 21

All except E

• Frequent shedding at oropharynx
• Latency in B lymphocytes

Question 22

For presistence and latency in Epstein-Barr virus, reactivation will occur in which 2 groups of patients?

Malignant diseases related?

Answer 22

1. Immunocompromised
2. Lymphoproliferative disorder

Malignancies

• NPC
• Burkitt’s lymphoma
• HL
• Gastric carcinoma
• NHL

Question 23

How is EBV diagnosed in:

1. Infectious mononucleosis in primary infection
2. Lymphoproliferative disease in immunocompromised
3. NPC ?

Answer 23

1. Infectious mononucleosis in primary infection
   - EBV VCA (viral caspid Ag) IgM
   - Monospot test: heterophile Ab test
2. Lymphoproliferative disease in immunocompromised
   - Histology (definitive)
   - EBV DNA viral load
3. NPC
   - Histology (definitive)
   - EBV IgA
   - Plasma EBV DNA

Question 24

HHV-5 name?

Answer 24

Cytomegalovirus

Question 25

Primary CMV infection in infants: A. Very common B. Contact at vaginal delivery, breast milk, saliva, urine C. Always asymptomatic D. Causes hepatomegaly, hepatitis, pneumonitis in adults E. In-utero infection may cause hearing and eye sight problem

Answer 25

D is wrong: should be in pre-mature infants Adults: mostly asymptomatic, occasionally with infectious mononucleosis E: outcome depends on primary infection/ reactivation in mother

Question 26

CMV persistence: frequent shedding from? | Latency at?

Answer 26

Salivary glands and kidneys ; Latency: hematopoietic progenitors > transmission: blood transfusion, organ transplant reactivation: opportunistic infection in immunocompromised

Question 27

CMV causes serious diseases in immunocompromised patients. What patients? What disease?

Answer 27

AIDS, transplant recipients, autoimmune disease, immune-suppressive therapy - Retinitis, enteritis, hepatitis, pneumonitis

Question 28

What is the problem of CMV-status mismatch in transplant/transfusion? e.g. CMV IgG+ donor to CMV IgG- recipient How to prevent?

Answer 28

Primary infection in immunocompromised: more severe disease than reactivation - Should do CMV- to -, + to + - should use leukocyte depleted blood

Question 29

CMV infection = CMV disease? T/F?

Answer 29

F - isolation of CMV does not mean suffering from disease - from tissue with pathology gives a better correlation but still not definitive

Question 30

In pregnant women and immunocompromised patients, primary infection is more serious than reactivation. T/F?

Answer 30

T - there is no reliable test to differentiate the 2 - CMV IgM and 4 fold rise in Ab occur in both - A prior serum to prove CMV IgG-ve to confirm primary infection (Appreciate the difficulty to diagnose CMV, dont jump to CMV + conclusion and give treatment, as it is quite toxic)

Question 31

HHV-6 = human herpesvirus type 6 A. affected 90% of us from 6 months to 2 years old B. transmitted via saliva C. Exanthem subitem: high fever > rash D. Febrile convulsion, hepatitis, lymphadenitis E. Persistence and Latency at B lymphocytes

Answer 31

E is wrong T lymphocytes and brain EBV is B lymphocytes

Question 32

HHV-7 A. Infection occurs later than HHV-6 B. Symptoms similar to HHV-6 to less frequently symptomatic C. Less well-defined association with reactivation in immunocompromised patients D. Similar epidemiology and clinical picture

Answer 32

All of the above

Question 33

HHV-8 A. T-lymphotrophic B. KS (Kaposi's sarcoma) in AIDS is more common in MSM C. KS in HIV-ve are more common in Mediterranean elderly men, immunosuppression in transplant D. All KS subtypes are associated with HHV-8 E. Virus is found in breast milk and saliva in endemic areas

Answer 33

All except A | should be B lymphotrophic

Question 34

In endemic area: HHV-8 A. Has both sexual and non-sexual route of transmission B. infection occurs in adults

Answer 34

B is wrong (should be non-endemic area) | infections occurs in early age, slowly increase with age

Question 35

Persistence = presence of virus in the body | Latent VS chronic?

Answer 35

Latent: presence of virus in an inactive site Chronic: presence of virus with active replication