Herpesviruses

Question 1

How many stains of herpesvirus is there?

Answer 1

8

Question 2

What are the 3 subfamilies of herpesviridae?

Answer 2

Alphaherpesvirinae
- HSV-1, HSV-2

Betaherpesvirinae

Gammaherpesvirinae

Question 3

Go over the structure of alphaherpesvirus.

Answer 3

From out to in:

Envelope proteins
Lipid envelope
Tegument
Nucleocapsid
DNA

Question 4

Go through the lifecylce of alphaherpesvirus.

Answer 4

Direct fusion to host cell
- entry of nucleocapsid and tegument proteins

Nucleocapsid movs to nucleus and inject viral DNA into host nucleus

Question 5

What entry receptors are used by alphaherpesviruses?

Answer 5

Herpes virus entry mediator (HVEM)
- primarily expressed on lymphoid cells (ex. T-cells)

Nectin-1

• ubiquitously expressed on many cell types
  
  • cell adhesion molecule

3-O-heparan sulfate
- modified form of heparan sulfate

Question 6

What strategies does Herpesvirus have for transcription (viral mRNA synthesis)?

Answer 6

Similar to poxvirus

immediate early (α)
 -  turn on the early (β) genes

early (β)
- encode for viral proteins that function in DNA replication

late (γ) gene expression
- encode for the structural proteins of the virus

Question 7

What is vp16?

Answer 7

a tegument protein

- activates transcription of the immediate-early (α) genes

Question 8

How does herpesvirus acquire its envelope?

Answer 8

Occurs by a double envelopment process.

The viral capsid is enveloped by the inner nuclear membrane as it translocates the capsid to the cytoplasm of the cell

The capsid then loses this initial envelope when it buds through the outer nuclear membrane

Capsid buds into Golgi (obtains new envelope)

Vesicle from Golgi containing the enveloped virion fuses with plasma membrane and enveloped virus released by exocytosis

Question 9

What are the clinical signs and symptoms of human herpesvirus?

Answer 9

Infection of the mouth, pharynx and genitals

Both cause latent infections

periodically reactivate from latency to cause lesions at or near the primary site of infection

Lesions of HSV-1 and HSV-2 look similar.

Question 10

What is Varicella Zoster Virus (VZV)?

Answer 10

Causes chickenpox and shingles

Question 11

WHat are the clinical signs of VZV?

Answer 11

Symptoms

• Fever and Malaise
• 300-400 lesions on the body during an attack.
• Blisters dry and form scabs in 4-5 days

Question 12

Go over the latency of herpesvirus.

Answer 12

HSV-1 and HSV-2 establish life-long latency in sensory neurons

No viral particles detected during latency

The virus hides for months or years until it is re-activated

Once reactivated, it travels the nerve pathway to the surface of the skin.

Question 13

How do you treat herpesvirus?

Answer 13

Most commonly prescribed drug is acyclovir
- Guanosine analog (ACG)

• Relatively nontoxic
• Can be used for long-term prophylaxis

Question 14

What glycoproteins are necessary for HSV entry?

Answer 14

gB
gD
gH
gL

Question 15

Go through HSV uncoating.

Answer 15

Nucleocapsid is released into cytoplasm

Some tegument proteins remain in cytoplasm

Other tegument proteins are transported to the nucleus
VP16 binds to DNA and is an activator of transcription

Question 16

Go over HSV attachment and entry.

Answer 16

gB and gC bind to cell surface GAGs to mediate initial attachment of virus to cells

gD binds with one of the co-receptors (HVEM or nectin-1)

Other glycoproteins mediate fusion of the virus envelope with a cell membrane
(plasma membrane or endosomal membrane)

Naked (de-enveloped capsids are deposited into the cytoplasm of the cell

Capsids next actively transported to the nucleus along microtubules

Question 17

What kind of genome does HSV have?

Answer 17

Linear dsDNA

Icosahedral capsid

Enveloped

Multiple glycoproteins