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Flashcards in Herpesviridae Deck (25):
1

List the 8 known human herpes viruses and their primary disease

HSV-1: keratitis, encephalitis, genital herpes, pharyngitis, skin ulcers
HSV-2: genital herpes, aseptic meningitis, neonatal herpes, pharyngitis
VZV: chicken pox, encephalitis, pneumonia, disseminated VZV
EBV: mono, Burkitt's, nasopharyngeal carcinoma
HCMV: heterophile negative mono, hepatitis, retinitis, colitis
HHV-6: roseola infantum
HHV-7: roseola infantum
HHV-8: Kaposi's sarcoma

2

Herpes viruses have 12 _____ in their envelopes and all have a tegument between the nucleocapsid and envelop

glycoproteins

the tegument plays a role in allowing the viruses to take over host cell machinery and initiate infection

3

Herpes viruses are divided into two categories based on tropism:

neurotropic (HSV-1, HSV-2, VZV) with tropism for nervous tissue and maintain a latent state in neurons

lymphotropic (HCMV, EBV, HHV-6, HHV-7) with ropism for lymphoid cells
- HCMV in monocytes
EBV in B cells
HHV-6 and HHV-7 in T cells

4

Herpes virus cause ____ infection of the host, meaning there are periods where no infectious virus can be isolated

latent

5

How do herpes viruses maintain latent infection?

They maintain their genomes as episomal elements that reside in the nucleus of the infected cell
The viral genome does NOT integrate into the host genome

6

Differentiate the mechanisms of latent infection in neurotropic viruses as as compared to lymphotropic viruses

Neurotropic: neurons are terminally differentiated and do not divide; virus can shut off expression of viral proteins to evade host immunity- expresses only latency associated transcript (LAT) mRNA which is not translated into protein

Lymphotropic: must express a minimal set of genes in dividing lymphoid cells in order to replicate and segregate appropriately. Avoid immune response by preventing MHC expression on the cell surface, encode mimics of immunosuppressive IL-4 and IL-10, encode decoy receptors, encode sequences that cannot be degraded and presented as antigens

7

Describe the sequence of herpes virus infection

- initial infection of epithelium at site of contact
- localized viral replication and uptake by sensory nerves
- virus loads onto microtubules for retrograde transport
- virus enters nucleus, circulizes
- if cell is permissive, productive infection begins
- newly assembled virions proceed by anterograde transport to the same site where infection was initiated

8

List some factors that re-initiate latent herpes infection

fever, stress, trauma, steroid hormone changes, UV light

9

How are herpes viruses transmitted?

close contact
EXCEPT: VZV can be spread by close contact and respiratory secretions

10

In general, seropositivity for herpes viruses in the population is (high/ low)

high
- HSV-1 90% by age 40
- HSV-2 is genital, increasing in prevalence
- VZV 90% by age 15, increasing with vaccine
- EBV and HCMV 90% in the population, common in day cares
HHV-6 and HHV-7: 90% positive by age 10. mild infections

11

How is latency of herpes viruses a problem for vaccine development?

Vaccines are generally designed to prevent symptoms, not infection

With herpes viruses, latency means that once you are infected, it is permanent

12

What are the most common manifestations of HSV-1 infections?

gingivomastitis in children- vesicles are very infectious

herpetic whitlow- HSV ulcers around the fingers of dentists

herpes gladiatorum- HSV ulcers on the cheeks, seen in wrestlers

Keratitis, leading cause of infectious blindness in the US. viral replication kills cells of cornea, each reactivation increases cloudiness

encephalitis, can be very serious wiht high mortality and serious sequelae. tx with antivirals

13

What are common manifestations of HSV-2 infection?

ulcers on genitalia, with tingling at the site and erythema

ulcers can be entirely internal in women

aseptic meningitis, usually self limiting

Neonatal herpes- highly lethal, must treat with antivirals

14

What are common manifestations of VZV?

Chicken pox- enters through respiratory route or direct contact of a mucosal surface, then disseminates and seeds the skin and internal organs

Vaccine has reduced incidence of chicken pox but has increased a new rash (highly attenuated, few lesions)

reactivation= zoster or shingles over one dermatome
--> post-herpetic neuralgia

15

What are common manifestations of HCMV?

cytomegalic inclusion disease: infants with hemolytic anemia, thrombocytopenia, hepatitis, splenomegaly, rash, mental retardation. highest risk if maternal HCMV infection occurs during pregnancy

heterophile negative mononucleosis- often subclinical

Immunocompromise: serious infection in organ transplant, blinding retinitis in AIDS, interstitial pneumonitis in BMT pts

16

List common manifestations of EBV

heterophile positive mononucleosis

Burkitt's lymphoma (c-myc regulates transition into S phase--> abnormal proliferation)

nasopharyngeal carcinoma in China

American Burkitt's

EBV lymphomas- post-transplant

oral hairy leukoplakia in HIV

Hodgkin's disease, GI cancers

17

List clinical manifestations of HHV6 and HHV7

roseola infantum- macular rash and mild fever, self-limiting in infants

can be a problem in immunocompromised/ transplant patients

18

List clinical manifestations of HHV8

Kaposi's sarcoma
- elderly men in Mediterranean
- spread by sexual contact
- common in AIDS

19

How are herpes infections diagnosed?

- simplex: appearance of lesions, culture of fluid, indirect immunofluorescnce, Tzanck test

VZV: appearance of lesions

EBV- monospot

HCMV: PCR, immunofluorescence, staining, immunohistochemistry, owl eyes on histology

20

What herpes viruses can be prevented with vaccine?

VZV- chicken pox and shingles

21

The first antiviral ever to be approved for treatment of a viral infection was _____ for topical application against HSV keratitis

idoxuridine

22

All currently approved antivirals act by targeting viral ______

polymerase

23

List two drugs that act by inhibiting viral polymerase

idoxuridine, triflurothymidine

24

List two drugs that act by causing chain termination during DNA synthesis and by inhibiting viral polymerase

acyclovir, valcyclovir

25

List two drug that are effective against HCMV

ganciclovir, foscarnet