Herpes Simplex Virus

Front 1

What are the two common related Herpes Simplex viruses?

Back 1

HSV-1 and HSV-2. The genomes of these two viruses are almost 50% alike.

Front 2

By the age of 18, approximately how many Americans will have been infected with Herpes virus?

Back 2

About 60%.

Front 3

Does HSV-1 have a specific target tissue of the body?

Back 3

Yes. The skin around the lips and the mouth are preferred targets.
HSV-2- Usually infects the genital area.
HSV-2 has already infected about 25% of the American population.

Front 4

Recently, it has been observed that about 40% of all new cases of oral herpes are caused by HSV-2 herpes. True/False

Back 4

True. Roughly, the same number of new genital herpes cases involve HSV-1.

Front 5

What specific type of cells does the Herpes virus invade?

Back 5

The epithelial cell. This is true especially of epithelial cells that are prone to constant physical contact. The virus produces rapidly in these cells.
New epithelial , as well as sensory neurons are targets after the virus starts its spreading mechanism.

Front 6

How does the Herpes virus initiate an infection?

Back 6

Being an enveloped virus, it possesses several proteins on its envelope. Glycoproteins such as gB and gC will bind to heparan sulfate, which is a carbohydrate on the proteins that make up the outer surface of every cell.

Front 7

Are there other glycoproteins involved in the initial binding mechanism?

Back 7

Yes. After the binding of the gB and gC, another gP called gD can bind to receptor proteins, such as nectin-1 on the cell surface.
The viral envelope will fuse with the cells plasma membrane, and its DNA viral capsid is released into the cytoplasm of the cell.

Front 8

The Herpes Simplex virus is a double stranded DNA virus that can code for more than 80 proteins. True/False

Back 8

True. In fact, Herpes virus has much more of a protein coding ability with respect to other viruses.

Front 9

Is there an advantage for the Herpes virus to code for so many proteins?

Back 9

Yes. It is required for three important features:
1. The ability to reproduce in cells that are not proliferating.
2. The ability to create a lytic type of burst in infected epithelial cells
3. The ability to create a hidden or latent infection in the nervous system.

Front 10

is there anything unique about the linear DNA genome of the Herpes virus?

Back 10

Yes. The linear DNA genome is enclosed in a protein capsid which is called a "tegument". This is a unique feature of the Herpes virus.
This tegument is enclosed in an envelope supplied by the host infected cell.

Front 11

What happens after the virus' envelope is shed at the cells plasma membrane?

Back 11

The virion will proceed to the cell nucleus where replication will take place. At this point, the capsid opens and the DNA is injected into the nucleus along with some of the tegument proteins.

Front 12

What happens once the genome is in the nucleus?

Back 12

Early viralmRNAs are transcribed and the DNA is replicated that produces many copies of the viral genome that are conjoined on a long linear DNA molecule.

Front 13

What happens to this large piece of DNA once it has been created in the nucleus?

Back 13

It will be used as a template for further viral mRNA synthesis before it is cleaved for the purpose of producing many copies of the linear viral genome.

Front 14

What happens to these newly created genomes?

Back 14

These new genomes are then encapsidated in the nucleus, and after the tegument proteins are added, the encapsidated DNA(nucleocapsid) buds through the nuclear membrane acquiring a temporary envelope.

Front 15

What happens after the nucleocapsid buds through the nuclear membrane?

Back 15

The temporary envelope is exchanged for another envelope before the finished viral particle, composed of viral DNA is released from the cell.

Front 16

Have DNA viruses acquired different strategies to make it possible for them to reproduce in resting human cells?

Back 16

Yes. Some DNA viruses(adenovirus) encode proteins that force resting cells to proliferate, thereby insuring that the enzymes and building block proteins that are necessary for for efficient viral reproduction will be available for their use.

Front 17

With respect to the previously discussed adenovirus, what mechanism can the Herpes virus employ for resting cells?

Back 17

The Herpes virus has genes which encode the proteins for DNA replication that are limited in resting cells. In addition to encoding its own DNA polymerase, it can also encode its own version of thymidine kinase.

Front 18

Why is thymidine kinase necessary?

Back 18

Thymidine kinase is required to produce large quantities of protein building blocks that are needed for the synthesis of new viral genomes.

Front 19

Can the herpes virus produce rapidly in cells?

Back 19

Yes. It can encode a protein, termed ICP27, which inhibits splicing of cellular mRNAs. Inibition of mRNA splicing helps focus cellular protein synthesis on the production of viral proteins. In fact, a single infected cell can produce thousands of new viruses within a 24 hour period.
Most Herpes virus DNA lack introns.

Front 20

What is an intron?

Back 20

An intron is any nucleotide sequence within a gene that is removed by RNA splicing while the final mature RNA product of a gene is being generated.

Front 21

What is an exon?

Back 21

An exon is any nucleotide sequence encoded by a gene that remains present within the final mature RNA product of that gene after introns have been removed

Front 22

How does the immune system protect other cells from viral attack, especially a Herpes attack?

Back 22

The genome of a Herpes virus has many unmethylated CpG dinucleotides which are not abundant in cellular DNA. This abnormal DNA is detected by TLR9 when the Herpes virus infects plasmacytoid dendritic cells that protect the epithelial cells surfaces. These toll like receptors then initiate a kinase cascade which results in the transcription of the genes for IFN-alpha and IFN-beta.

Front 23

What is the function of the Interferon after it is produced?

Back 23

It can bind to Interferon receptors on nearby cells and activate the expression of Interferon stimulated genes.

Front 24

Give an example of how a cell might be protected from viral attack.

Back 24

An Interferon stimulated gene, PKR for example, can bind to a double stranded RNA and phosphorylate eIF2-alpha, which is a protein necessary to initiate protein synthesis.
When eIF2-alpha is phosphorylated, protein synthesis ceasses resulting in the death of the infected cell, and all of the viruses in it.

Front 25

How can the Herpes virus protect itself against this cellular defense mechanism?

Back 25

It can create a defensive protein, termed ICP34.5. This protein made early in infection. It designs the dephosphorylation of eIF2-alpha, which allows the protein synthesis to continue.

Front 26

Can the Herpes virus protect itself against the complement cascade?

Back 26

Under normal conditions, complement proteins attach to viral surfaces. This prepares the virus through opsonization, to be ingested by macrophages. The viral protein gC binds to complement proteins and disturbs their function.

Front 27

How can the Herpes virus evade antibody attachment?

Back 27

The Herpes envelope has proteins that bind to the Fc region of IgG antibodies, the part which normally attaches to a macrophage. The antibody is unable to form a connection between the virus and the phagocyte.

Front 28

Can the herpes virus evade killer T cells?

Back 28

Yes. Shortly after infection, there is production of a viral protein, ICP47 which interferes with a TAP transporter system, and causes the destruction of class 1 MHC molecules, and makes it less probable that the killer T cells will recognize the infected cells.

Front 29

Why does Herpes virus' establish a latent infection in nerve cells?

Back 29

During a latent infection in nerve cells few Herpes proteins are produced. This is not the case in endotheial cells, where more than 80 proteins are made.
Nerve cells produce few class 1 MHC molecules.
Latently infected nerve cells are rarely destroyed by killer T cells.

Front 30

How does the viral genome exist in nerve cells?

Back 30

It exists as a free floating piece of DNA which is not associated with a host chromosome. Sensory nerve cells really dont proliferate, so if the Herpes DNA were integrated into the genome, it would be trapped there.

Front 31

How is herpes reactivation activated?

Back 31

It is activated by genes that are expressed within tently infected nerve cells. Episodes of reactivation are triggered by external factors, such as physical trauma, fever, U/V light, sexual activity etc.

Front 32

Is it true that many reactivation events are unsymptomatic?

Back 32

Yes. Virus shedding is actually a chronic process. It is occurring even in asymptomatic individuals.

Front 33

Can herpes be spread to other parts of theody?

Back 33

Yes. It can be spread via the fingers to the eyes. Corneal herpetic lesions are somewhat of a common finding in Herpes resident people.

Front 34

Are newborns prone to herpes infections?

Back 34

Yes. These infections occur mostly during birth, as the baby is being bathed in virus containing genital secretion from an infected mother.
It can spread to organs such as the adrenal glands, the liver and lungs. It is frequently lethal.