Herpes Simplex Viruses 1 and 2

Question 1

As a family, herpesviruses are

Answer 1

Large, double-strand DNA viruses whose icosahedral capsids are surrounded by lipid envelopes.

Question 2

Herpesviruses are complex, encoding over 90 proteins that supply:

Answer 2

Attachment and fusion glycoproteins of the envelope; transcriptional regulators that redirect host RNA polymerase to viral genes; a viral DNA polymerase and associated enzymes for replication of the virus genome; capsomeres; and still other envelope glycoproteins required for virus spread from cell to cell.

Question 3

A hallmark of herpesviruses is their ability to?

Answer 3

Establish latent infections in which the virus genome, but not virus progeny, is maintained in a quiescent state for the remainder of the host’s life.

Question 4

Once infected with a herpesvirus?

Answer 4

A patient is infected for life and subject to recurrent infections when the latent virus reactivates to produce progeny once again.

Question 5

Herpes simplex virus (HSV) serotypes 1 and 2 can be transmitted?

Answer 5

Sexually-transmitted viruses

Question 6

HSV 1 and 2 replicate in?

Answer 6

Epithelial cells and reside latently in the trigeminal or sacral ganglia hence, they are termed neurotropic herpesviruses.

Question 7

While HSV 2 principally causes?

Answer 7

Genital lesions, HSV 1 can too, and both viruses cause additional ailments.

Question 8

Once attached, HSV directly fuses with the plasma membrane in a

Answer 8

pH-independent manner and the released nucleocapsid migrates to the cell’s nucleus where the genome is released.

Question 9

Initial transcription/translation (“immediate early” expression) produces proteins that act

Answer 9

As transcriptional regulators that modify host RNA polymerase so that it preferentially transcribes viral genes over host genes.

Question 10

“early” proteins whose roles are

Answer 10

To replicate the virus genome to produce progeny genomes.

Question 11

Prominent “early” proteins include

Answer 11

A thymidine kinase and components of a virally-encoded DNA polymerase.

Question 12

The thymidine kinase is important clinically for two reasons?

Answer 12

First, it is required to phosphorylate (and hence activate) acyclovir (ACV) and derivatives, the drugs of choice to treat most HSV infections. Second, thymidine kinase mutants are a problem during treatment because their spontaneous occurrence renders HSV resistant to ACV.

Question 13

HSV resistant to ACV is particularly a problem in

Answer 13

AIDS patients dually infected with HSV.

Question 14

The “late” class of proteins is produced; these encode the?

Answer 14

Capsomeres, envelope glycoproteins, and other structural proteins.

Question 15

Virus assembly occurs in the?

Answer 15

Nucleus and the virus buds from the plasma membrane during release.

Question 16

Because the same viral glycoproteins responsible for the initial fusion (entry) event are?

Answer 16

Also present in the plasma membrane of infected cells late in infection, infected cells may fuse with adjacent, uninfected cells.

Question 17

HSV can spread from cell to cell without?

Answer 17

The formal release of virus progeny from one cell and subsequent attachment and penetration of a nearby cell leading to the formation of syncitia: giant cells with more than one nucleus.

Question 18

Virus assembly in the nucleus and syncitium formation are the basis of?

Answer 18

A diagnostic test for HSV: the Tzanck smear, in which smears of cells taken from an ulcerous lesion (vesicle) are viewed under a microscope.

Question 19

Nuclear assembly leads to the formation of?

Answer 19

Inclusion bodies in the nucleus.

Question 20

If a Tzanck smear reveals multinucleated giant cells with nuclear inclusion bodies?

Answer 20

The infection is caused by a herpesvirus, presumably HSV.

Question 21

Soon after primary infection in epidermal cells, HSV?

Answer 21

Establishes latency in peripheral sensory neurons.

Question 22

Once latency established, the entire virus genome is?

Answer 22

Maintained extrachromosomally in neurons in 10-100 copies per cell, much like a plasmid in bacteria.

Question 23

The only HSV gene expressed during the maintenance of latency is called?

Answer 23

LAT (latency-associated transcript) whose product is an RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron.

Question 24

Because only LAT is expressed?

Answer 24

No virus particles are produced during the maintenance of latency.

Question 25

A decline in cell-mediated immunity allows the virus to?

Answer 25

Reactivate from latency and begin a productive, lytic replication cycle.

Question 26

Reactivation of the latent virus in neurons leads to?

Answer 26

A recurrent infection in epithelial cells innervated by the latently-infected neurons.

Question 27

Frequent sufferers of cold sores will often complain of numbness at the site after many years of recurrences.

Answer 27

Reactivation apparently kills the neuron

Question 28

HSV 1 Diseases:

Answer 28

Gingivostomatitis
Herpes labialis (fever blister) 
Herpetic whitlow (finger vesicle) 
*Keratitis* 
Conjunctivitis 
Blepharitis 
*Encephalitis*

Question 29

HSV 2 Diseases:

Answer 29

Cervicitis
Vulvular vesicles
Vaginal vesicles
Urethritis (rarely)
Penile vesicles
Perianal vesicles
Meningitis
Encephalitis

Question 30

As with most viral infections, HSV infections are generally?

Answer 30

self-limiting.

Question 31

Skin, ocular, and urogenital infections can be caused by?

Answer 31

Either virus, thus HSV 1 is not strictly limited to “above the belt” nor HSV 2 limited to “below the belt.”

Question 32

Disseminated disease is a problem among?

Answer 32

Immunocompromised patients, often from reactivation. Neonates are also at risk can be severe or fatal.

Question 33

A significant percentage of primary HSV infections are?

Answer 33

Asymptomatic.

Question 34

When infections are symptomatic?

Answer 34

Multiple blisters form on the infected skin (oral, genital, or perianal) about two weeks following infection.

Question 35

The blisters soon rupture producing?

Answer 35

Mildly to somewhat severely painful open vesicles (ulcers) which will take up to two weeks to heal during a primary infection.

Question 36

Recurrent infections occur during lapses in?

Answer 36

Cell-mediated immunity and the resulting cold sores or genital lesions are limited in size and duration due to the presence of neutralizing antibody.

Question 37

Transmission:

Answer 37

Both HSV 1 and 2 can be transmitted sexually although HSV 2 is the more frequent genital infection.

Question 38

Epidemiology HSV 1:

Answer 38

Up to 60% of the adult US population has been infected with HSV 1.

Question 39

Epidemiology HSV 2:

Answer 39

Most HSV 2 infections are diagnosed between the ages of 20 and 29; rates are 10% in adult males, 20% in adult females, and 10% in young adults.

Question 40

If a mother presents with herpetic lesions at delivery?

Answer 40

The baby should be taken by C-section.

Question 41

Diagnosis of oral herpes is generally by?

Answer 41

Clinical appearance.

Question 42

Diagnosis Genital herpes:

Answer 42

Culturing virus from lesions;
Fluorescent antibody (FA) screening 
PCR screening
Serology:
Tzanck smear:

Question 43

Once individuals are infected with HSV?

Answer 43

They are infected for life. There are no curative treatments, but fortunately, there are several good antiviral treatments to lessen disease episodes.

Question 44

There are four major groupings of anti-HSV drugs:

Answer 44

Acyclovir (ACV): drugs of choice
Vidarabine and trifluoridine
Foscarnet (Phosphonoformate)
Docosanol

Question 45

Vidarabine and trifluoridine mechanism:

Answer 45

DNA base analogs that inhibit the viral DNA polymerase.

Question 46

Foscarnet (Phosphonoformate) mechanism:

Answer 46

Pyrophosphate analog that blocks the pyrophosphate-exchange site preferentially on the viral DNA polymerase.

Question 47

Docosanol mechanism:

Answer 47

Modifies the host cell membrane so that the virus envelope cannot fuse with the plasma membrane, thus limiting the spread of the reactivated virus.