Common Viral Pathogens - Herves Virus

Question 1

Herpes Simplex -1 (HSV)

Target cell type, latency, transmission and clinical manifestations

Answer 1

Target cell type: mucosal epithelium

Latency: neuronal ganglion

Transmission: close contact

Clinical manifestations: Orofacial lesions and some genital lesion
Encephalitis
Herpes whitlow
Herpes keratitis
Neonatal herpes

Question 2

Herpes Simplex -2 (HSV)

Target cell type, latency, transmission and clinical manifestations

Answer 2

Target cell type: mucosal epithelium
Latency: neuron ganglia Transmission: close contact (usually sexually)
Clinical manifestations:
Genital lesions and some (orofacial lesions) -> encephalities, herpes whitlow, herpes ketaritis, neonatal herpes

Question 3

Varicella Zoster Virus

Target cell type, latency, transmission and clinical manifestations

Answer 3

Target cell type: mucosal epithelium
Latency: neuron ganglia
Transmission: contact or respiratory route
Clinical manifestations: Chickenpox (varicella) and shingles (zoster)

Question 4

Epstein-Barr Virus (EBV)

Target cell type, latency, transmission and clinical manifestations

Answer 4

Target cell type: B lymphocytes, epithelia
latency: B-lymphocytes
transmission: Saliva
clinical manifestations: Infectious mononucleosis, Burkitt’s lymphoma, in immunocompromised patients, central nervous system lymphoma

Question 5

Cytomegalovirus (CMV)

Answer 5

Target cell type: epithelia, monocytes, lymphocytes, others
Latent cell types: monocytes, lymphocytes and others
Transmission: contact, blood, transfusions, transplantation, congenital
Clinical manifestations: infectious mononucleosis-like syndrome:
In immunocompromised retinities, pneumonia, colitis. IN new borns: congenital CMV

Question 6

What kind of virus are herpes viruses

Answer 6

dsDNA protected by an icosahedral capsid. Nucleocapsid is further surrounded by glycoprotein rich envelope. - establishes latend infection in the host and may get reactivated later.

Question 7

Herpesvirus entry/nuclear transport

Answer 7

Attach and bind to surface proteins ofund on host cell causing fusion of viral and host membranes. Neocleaocapsid is realeased, transported into the nucleus via cellular microtubuls where the genome enters through the nuclear pores.

Question 8

Hespesvirus replication

Answer 8

Immediate early (IE) genes are expression prior to protein symthesis -> required for the expression of the early (E) and late (L) genes, which are synthesized de novo.

E genes encode proteins involved in DNA repocation (like DNA polymerase, etc.)

L genes encode structural proteins, such as capsid and glycoproteins.

Question 9

Herpesvirus assembly and egress

Answer 9

Occurs in the nucleus. Capsids self-assemple and newly synthesized DNA gets packaged.

Nucleocapsids bud through nuclear membrane and acquire their glycoprotein-rick envelope as they pass through GOLGI COMPLEX.

Leaves via exocytosis or cell-lysis.

Question 10

Incubation period of HSV-1 or HSV-2

Answer 10

2-12 days (average is 4 days)

Question 11

HSV-1 and HSV-2 latent ganglions

Answer 11

For orofacial lesions, trigeminal ganglion

For genital lesions, sacral ganglion

Question 12

Location of reoccurent HPV-1 and HPV-2

Answer 12

Face (orofacial)
Cornea (keratitis)
Perineum (genital herpes)

Can be reactivated by a variety of stressors

Question 13

Gingivostomatitis

Answer 13

HSV-1 primary infection, child develops painful mouth vesciles and ulceration sof the gums,lips and tongue. Ulcers in the anterior art of the mouth. Fever. Swelling of lips/drooling. Cervical lymph node swelling

Question 14

Herpatic whitlow

Answer 14

inocculation of HSV from oral seretions onto the fingers -> gains access into the skin via small cut.
Occupational hazard.

Eythema, swelling and grouped vesciles on an erythmatous base. Not a bacterial infection.

Mother kissing baby’s hurt finger

Question 15

Genital herpes

Answer 15

sexually transmitted infection that is usually caused by HSV-2 (some HSV-1, 30%)

Very painful lesions that last 10-14 days

Question 16

Herpes keratitis

Answer 16

HSV infects the cornea o the eye. More common from HSV-1. Produces dendritic lesions of the cornea, which can cause scarring and blindness.

Question 17

Encephalities

Answer 17

can be caused by primary disease or reactivation. Can occur through blod-orne spread or neuronal transmissin of the virus. Infection of the brain is fulminant and hemorrhagic, necrotizing encephalities.

Predcilection to the temporal lobes of the brain. Altered mental status. Mortality 30% w/ treatment.

Question 18

Neonatal herpes

Answer 18

primary inftion of the neonate that can be acquired intrauterine, peripartum or postpartum. (most during peripartum) Most caused by HSV-2 due to genital lesions.

Three forms of disease.

1) skin, eye and mucous membrane (SEM)
2. ) CNS
3. ) disseminated

disseminated is the most severe, finding vescile in neonates less than 4 weeks is a medical emergency. Herpes is high on this differential.

Question 19

Herpes labialis (cold cores)

Answer 19

Most common symptomatic reactivation associated w/ HSV-1.

Very common and self-limited

Question 20

Diagnosis of HSV infections

Answer 20

Gingivostomatitis and herpes labialis can be diagnosed clinically, as well as genital herpes.

Viral culture of lesions
Direct flourescent antibody staining
PCR of lesions

Question 21

Treatment of HSV

Answer 21

Nucleoside analog drugs treat herpes, take advantage of viral enzyme thymidine kinase

aceclovir the most common. Severe HSV infections treated w/ IV acyclovir.

Question 22

HSV prophylaxis

Answer 22

In certain paritents, oral antiviral suppressive therapy is good for frequent painful oral or genital reoccurences. Must be able to take medicine one or twice daily.

Question 23

Chickenpox (varicella)

Answer 23

highly contagion common childhood disease. Transmitted by respiratory route or direct contact. Contagious for 102 days before the rash appears and until all blisters have formed scabs.

Incubation period. 10-21 days

Symptoms: fever, malaise… rash appears in “waves.” Lesions mature. Rash appears on face or trunk, spreads to extremities. LESIONS IN VARIOUS STAGES OF DEVELOPMENT. Itchy. Takes about 7 days for all lesions to scab.

Question 24

Pathogenesis of chickenpox

Answer 24

virus gains enty via respiratory tract, spreads to regional lymphoid system. Replication takes place in lymph nodes in 2-4 days, and primary viremia 2-6 days after initial infection. Virus replicates in liver, spleen, and then you have a secondary viremia. Spreads to skin 14-16 days after initial exposure.

Question 25

Complications of chickenpox

Answer 25

1. ) Secondary infection or cellulitis - Group A step most common. Keep lesions clean.
2. ) Pneumonia - bacterial pneumonia from group A strep or staph. Viral pneummonia - immunocompromized patients or pregnant women. Very serious.
3. ) necrotizing fascitis - rare. Infection profresses along fascial planes, shears off nerve endings and blood suplly to skin causing cell death. Usually due to group A strep.
4. )Encephalities or encephalomyelitis - occurs during convalescent stage of varicella and is through to be antibody mediated. It occurs 2-3 weeks after illness, likely due to cross reacting antibodies with briain antigens. ANTIBODY MEDIATED DISEASE
5. )Hepatities - mild elevations of liver function tests sometimes seen. Only in immunocomromised hosts.
6. ) Congenital varicella syndrome - RARE, pregnant woman in ger first 8-20 weeks of pregnancy. Fetus exhibits multiple tissues and organ abnormalities, such as microcephaly, mental retardation, hypoplasia, hypopigmentation, etc.

Question 26

Treatment of varicella

Answer 26

Usually self limiting in children, but if given within 2-3 days antiviral therapy can shorten the course. Acyclovir is chosen treatment.

Question 27

Prophylaxis of chickenpox

Answer 27

Live attenuated varicellar zoster virus vaccine is given to chingren in a 2-dose series via subcutaneous injection

1st dose at 12-15 months
2nd dose at 4-6 yrs

Contraindicated in immunocompromised patients (including pregnant women)

Question 28

VZV Latency and Reactivation

Answer 28

Virus migrates to cerebral or dorsal root ganglion, remains there for a time period (some may be life long.) 1/3 of affected individuals have virus reactivation which results in shingles.

Produced varicella-like rash on the associated dermatome. DOES NOT DISPLAY ASYMPTOMATIC VIRAL SHEDDING.

Lowered cell mediated immunity is critical part of putting people at risk for shingles

Question 29

Shingles

Answer 29

Radicular pain in the area of activated nerve. Lesions are grouped vesicles on an erythmatous base. Confined to single dermatome! Do not cross midline. Lesions heal in about 2 weeks. Can affect eye via trigeminal nerve. Pain may last weeks/months: post-herpatic neuralgia

Question 30

Diagnosis of Shingles

Answer 30

Usually diagnosed clinically.

Direct flourescent antibody
VZV polymerase chain reaction
Viral culture

Question 31

Treatment of Shingles

Answer 31

Acyclovir given within 48-72 hours of onset may decrease lesions and pain. Pain needs to be controlled from post-herpatic neuralgia.

Question 32

Shingles prophylaxis

Answer 32

a shingles vaccine (Zostavax) approved for people 50 yrs old or older, live attenuated vaccine and given as 1 dose. Boosts immune response to VZV and decreases likelihood in developing shingles.

Question 33

Cytomegalovirus

Answer 33

Infects the majority of people by adulthood. Infection may occur in utero, perinatally, or postnatally.

Question 34

Cytomegalovirus transmission

Answer 34

Infected body fluids

Saliva, breast milk, sexual contact, blood, tears, respiratory secretions. Blood.

Question 35

Cytomegalovirus incubation period

Answer 35

2 weeks to 2 months

Question 36

Cytomegalovirus pathophys

Answer 36

CMV enters epithelial cells of salivary gand or the genital tract, persistent infection with intermittent viral shedding. Likely viremia causing wide distribution of virus. Can be shed in urine.

Question 37

CMV primary infection

Answer 37

Usually asymptomatic. If symptoms occur, can take 2 forms

1. ) mild febrile illness or
2. ) mononucleosis-like illness with fever, swollen lymph nodes and mild hepatitis.

Question 38

CMV latency and reactivation

Answer 38

virus remains latent for life, may be reactivated from time to time when infection is spread through urine or saliva. Reactivation in immunocompromised people may cause pneumonia, colitis, hepatitis, encephalitis, etc.

Question 39

Pregnancy and CMV

Answer 39

pregnant woman develops primary infection, 3-5% chance child born w/ congenital CMV infection.

10-15% of the infected infants will have symtpms at birth.

Congenital CMV: low birth weight, microcephaly, hearing loss, mental impairment, hepatosplenomegaly, skin rash (blueberry muffin spots) jaundice, etc.

Question 40

Diagnosis of CMV

Answer 40

Viral culture
PCR
Flourescent antibody staining
Serology (can test whether the person has EVER had CMV, whether its recent, or activated)

IgM+, IgG- =acute CMV disease
IgM-, IgG- = never infected with CMV
IgM-, IgG+ = patient has previously been infected
IgM+, IgG+ recent CMV reactivation

Question 41

CMV histology

Answer 41

Characteristic “owl’s eye” appearance, which is diagnostic. Dense, dark nuclear body surrounded by a halo.

Represent intranuclear inclusions.

Question 42

Treatment for CMV

Answer 42

In healthy people, no treatment

Immunocompromised = antiviral, Ganciclovir. CMV-IG, an immunoglobulin preparation with high titer of CMV antibodies, together with Ganciclovir are sometimes used to treat CMV pneumonia

Question 43

Prophylaxis for CMV

Answer 43

No available vaccine. CMV-IG given intravenously monthly to severely immunocompromised patients who are at high risk .