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Flashcards in Herpes Viruses Deck (41):
1

What is the genome of herpes viruses?

 

What is the composition of the virus?

double stranded DNA with linear genome

 

Enclosed in capside surrounded by tegument which is surrounded by lipid envelope

 

There could be unique isoforms of the UL and Us sections

2

What is the sequence of transcriptional events?

 

Burst of RNA synthesis for proteins needed at that time; proteins are transcribed from genomes within the virion

Early proteins synthesized a responsible for DNA synthesis a then DNA rep then all the virion structural proteins produced and assembled into virus particles.

3

What does the primary infection for HSV1 include (6)

 

Means of transmission? 

Portal Entry?

Target cell?

cold sores, sore throat, fever, rarely encephalitis.

less freq found as a genital infection

Also could cause herpetic keratinitis

 

Transmission: direct contact

Portal of entry: mucosal membranes, skin 

Target: skin

Primary lytic infection of epithelial cells

4

What is the pathogenesis of herpes?

1. Primary lytic infection of epithelial cells

2. Virus infects sensory neurons [latency]

 

Latency associated transcrips (LATs), are the only viral mRNA that will be present in sensory root

Reactivation can occur --> virus travels back to epithelial cells causing lesions and shedding (at same site of primary infection)

5

HSV1: What is occuring during the latent infection period?

 

What occurs during recurrence?

Asymptomatic, no virus are being produced (thus NOT chronic)

Viral NDA resides in SENSORY CELLS of TRIGEMINAL NERVE GANGLION!

 

wait for reactivation (stress, immunosuppression...) 

 

Reccurent infection: virus replicated and travels down sensory nerve fibers to infect epithelial cells around the NOSE AND MOUTH

 

Symptoms are usually milder for of primary infection

6

What is the primary infection of HSV2?

Usually vesicular eruptions on the genitalia, less frequently found as herpes labialis (cold sores)

 

Transmission: (sexual) contact

affects both sexes

 

7

Latent infection and

Recurrent infection of HSV2?

During latent infection, no virus are being produced. Viral DNA resides in SENOSRY CELLS of SACRAL GANGLION

 

Recurrent Infection: milder outbreak generally in same location in genital area

[could occur monthly for some women]

8

Other HSV lesions: 

Herpatic whitlow?

Gladitorium?

Whitlow - associated with herpes on the fingers/abrasion in the fingers; usually seen in dentist, or emergency workers (HSV1/2)

 

Gladitorium - associated with wrestlers / gyms (HSV1)

 

Ocular herpes - keratoconjuctivitis (HSV1)

 

less common but can occur due to specific contact with infectious agent in different body locations

eonatal herpes, encephalitis (primary or reactivation), disseminated herpes

9

What is one treatment option?

What are 2 awesome things about this drug?

HSV - acyclovir (nucleoside analog- chain termination by substituting GTP into DNA strand)

 

Unphosphorylated and becomes phosphorylated in virally infected cells! (via viral thymidine kinase)

Higher affinity for herpes virus DNA polymerase than cellular

10

Could acyclovir resistance develop?

How do mutations arise?

Resistance is due to mutation in the gene encoding 

*viral thymidine kinsae, the drug is not phosphorylated to the active form

* viral polymerase - the polymerase no longer efficiently binds the drug

 

Doesn't happen often, usually the viruses are still attenuated, and more likely seen in immunocompromised patients

11

Pritelivir:

MOA

Directed towards herpesvirus helicase-primase (involved in the unwinding of the DNA)

Stop DNA rep

Specific to herpes virus

 

--> shown to REDUCE SHEDDING and REDUCE DAYS WITH LESIONS

 

12

Varicella Zoster Virus:

 

Primary infection (3)

1. infection occurs in seasonal epidermics as chicken pox (varicella)

2. Contracted from another infected individual usually a child, via RESPIRATORY TRANSMISSION

3. Systemic infection resulting in a generalized, vesicular rash

 

Mild prodrome (fever and malaise) for 1-2 days

Successive crops (2-4 days) of pruritic vesicles

Generally appear first on head, most concentrated on trunk

generally mild in healthy children

 

** you see the vesicles at all different stages!!**

13

When/how can the virus be transmitted?

Usually infectious stage BEGINS durring the prodrome stage of the virus, BEFORE the vesicular rash appears; infeciton of mucosa of upper respiratory tract

 

Primary viremia begins around day 5 --> viral replication in liver, spleen and other organs --> secondary viremia = contagious period (around day 11) --> Fever --> infection of skin and appearance of vesicular rash at about day 14, where the individual is still contagious

(contagious from days 11 - 17)

 

Overall about 20 day cycle

14

What can scratching a lesion impose?

scratching --> infection with s. aureus

15

What are the complications of varicella? (5)

 

What age group are these complications mostly seen?

Bacterial infection of lesions

CNS manifestations (encephalitis)

Pneumonia (rare in children)

Hospitalization ~3 per 1000 cases

Death ~1 per 60,000 cases

 

Especially seen in infants under 1 or adults over the age of 30 who acquire primary infection

16

What vaccine is available for vzv?

 

What is its effectivness

 

Who shouldn't receive it and why?

VARIVAX

 

Live-attenuated vaccine (not to be given to immunocompromised hosts)

95% efficacy [98% effect in protecting from severe dz, 70-85% protective against any form of VZV]

induces seroconversion after 1 dose

duration is probably life long

Now given as: MMRV, thus boosted every so often

17

VZV latent infection and recurrence?

 

presentaiton?

Latent: asymptomatic with no virus or virion proteins produced, viral DNA resides in the cells of the DORSAL ROOT GANGLIA

 

Recurrent: virus travels down the sensory nerve fiber and infects epithelial cells inundated by the fiber

Painful, unilateral vesicular eruptions localized to the dermatome, usually in head or upper trunk

Severe systemic infections are observed in immune suppressed individuals

18

Protection for the elderly?

VZV vaccine - reduces incidence of herpes zoster (postherpetic neuralgina) 

 

19

What could you do about protecting immunocompromised individuals?

varicella-zoster IMMUNE GLOBIN

provides PASSIVE IMMUNITY

 

but this cannot induce lifelong immunity; thus should be immunized as soon as person gets out of their immunocompromised state

20

Can shingles be infectious?

generally not as much - it is not through respiratory but rather the viral particles are in the vesicles themselves. Most of the time they are covered up and not being touched and passed on. 

21

dx:

herpes encephalitis

HSV 1 /2

VZV

EBV

CMV

HHV 6 & 7

HHV 8

 

herpes encephalitis - PCR

 

HSV 1/2 -- clinical but also PCR

 

VZV - clinical

 

EBV - monospot (and/or serology for IgM to VCA)

 

CMV- PCR, serology, histology

 

HHV 6&7 - clinical 

 

HHV 8 - clinical, PCR

 

22

EBV: 

 

Primary Infection Clinical presentation?

 

Malignant lyphoproliferative dz?

 

younger you are, the less symptomatic it will be 

kissing disease -  teenagers come in with mono

 

Primary infection: asymptomatic, infectious mononucleosis (mono)

 

Malignant lymphoproliferative dz:

burkitt's lymphoma, nasopharyngeal CA

 

EBV antibodies can be found in about 95% of most of the adult population

EBV can be isoalted from teh thorat washing of acutely ill pt and excretion may continue intermittently for months after all signs of illness have disappeared!

23

EBV transmission?

 

Who is at highest risk? 

 

When do we see it most often?

 

What does this cause?

Saliva! 

 

Teenagers adn adults at highest risk for infectious mono

also, ppl with T-cell deficiencies!

 

See world-wide with NO SEASONAL incidence

causes life-long infection; asympo shedding of virus

24

What is the mxn of dz of EBV?

Virus in saliva infects epithelia and spreads to B-CELLS in lymphatics

 

Infection promotes GROWTH of B-cells [cause them to spew out any antibody B cells are making]

T-cells kill/control B-cell outgrowth --> promote LATENCY IN B-CELLS

Severe disease in T-CELL deficient patients

25

What is something particular about the B-cell antibodies?

 

T-cells?

You will see heterophile antibody = lots of different antibodies produced because so many are activated -- antibodies produced against weak antigens 

 

You will also see DOWNEY CELLS - atypical lymphocytes

(seen on blood smears)

26

How do you detect EBV infection?

1. Monopsot test: 

detection of heterophile antibodies 

false negative 5-15%, esp in children!!

 

2. Antibody to EBV VCA

IgM/IgG to viral capsid antigen

more specific test than monospot test, less false neg.

27

What is the serology look like through the course of EBV infection?

 

Initial - resolution - convalescence ?

Primary - IgG and IgM to viral capsid

down --> antibodies to early antigen

 

Sign of resolution - antibody + EBV and nuclear antigen (indicative of resoution of disease)

 

Convalescent serology: IgG+ for VCA but IgM- for VCA

 

28

Sx of primary EBV: (5)

 

Tx?

fever, malaise, lymphadenopathy, hepatosplenomegaly, pharyngitis

 

During this time, virus is in the saliva!

no sharing stuff!

 

TX: no treatment

(acylovir does not work, no vaccine!)

29

What are the most common clinical syndromes of EBV? (6)

Early age - asymptomatic

Infectious mononucleosis

Post-transplant lymphoproliferative disorder (PTLD)

Hairy oral leukoplakia w/AIDS

African Burkitt's Lymphoma (malaria is a co-factor)

Nasopharyngeal carcinoma (CHINA!)

30

CMV

Primary infection (6 clinical prez)

VS

Carrier state

Primary infection:

asymptopmatic infection 

BUT fetal/neonatal infection CAN BE VERY SERIOUS!!

mono (10%!), AIDS retinitis and pneumonitis, post-transplant pneumo

 

Persistent Infection/carrier state:

Asymptomatic shedding

serious complications in immuno-compromised pt

31

what is tricky about CMV ?

Could also cause mononucleosis!

 

But it with be heterophile Ab negative

VAC negative

32

How is AIDS/Immunocompromised CMV infection best controlled?

Restoration of T-cells!

33

Cytomegalic Inclusion Disease/Neonate Infection:

 

Mother's CMV state?

Seronegative mother that has a primary infection during pregancy

 

pneumonia, CNS, calcifications...

34

How is CMV transmitted? How does it infect? Where does it remain latent?

 

Who is at highest risk?

Transmissions include: blood, secretions - breast milk, semen

[mostly acquired in childhood, most secretions are via cervical - potential for CMV secretions increase in the third trimester of pregnancy]

 

--> productive infection of epithelium --> establishes latency in T-cells, macrophages, lymphocytes...

 

Highest risk: babies and immunosuppressed individuals; suppression of cell-mediated immunity allows for recurrence!

35

How do we test of CMV?

PCR - detection of CMV DNA

 

Serology - CMV specific IgM and IgG

 

Cytology/histology - Owl eye inclusion body

36

CMV treatment (2) 

Ganciclovir: (nucleoside inhibitor)

- Activated CMV-infected cells

-PROBLEM: bone marrow toxicity (est stem cell translplant pt!)

 

Letermovir: (not yet FDA approved *NEW*)

Prophylaxis in hematopoietic cell transplant

RED incidence of CMV in transplant pt

Targets CMV terminase complex (CMV specific)

Dose-dependent inhibition

37

What causes Roseola?

 

SX: (5)

 

Recurrence/latency?

HHV 6 adn HHV 7

 

Rapid onset of HIGH FEVER, generalized rash 24-48 hours AFTER fever, T-cells resolve infection --> virus becomes latent T cells

Unknown if there is actual recurrence!

 

95%  of people are seropositive for HHV6/7 by the age of 5

38

Transmission/pathogenesis

 

Clinical DX?

Respiratory Transmission -- incubation period of 4-7 days

ABRUPT HIGH FEVER (103-105) 2-4 days

AFTER fever --> erythematous lace-like RASH all over body while sparing the face 1-2 days

Receovery withouth complications

 

NO rapid test! Clinical diagnosis

no therapy, no vaccine

39

What causes kaposi's sarcoma?

 

Who is a higher risk?

 

What does the typical lesion look like?

HHV 8

 

YOU MUST BE IMMUNOSUPPRESSED

it is the most common neoplasm in AIDS pt

Seen also at INC in elderly men of mediterranean/eastern european descent (Russian), and endemic in Africa

Iratogenic in post-transplantion

 

Red/violacious lesion anywhere on the body

Spindle-shaped tumor cells, neovascularization, inflammatory infiltrate

40

TX?

1. Restore T cell function (esp in AIDS pt!) in order to control

activation of KS during immunosuppression; in HIV pt use antiretroviral durgs reduces/controls KS

 

NO OTHER DIRECT TREATMENT OF KS!

41

Transmission?

Sexual transmission (MSM)