Herpes Simplex Viruses

Question 1

What viruses fall in the herpes virus group?

Answer 1

HSV-1, HSV-2
Varicella zoster virus (VZV)
Cytomegalovirus (CMV)
HSV-6,7
Epstein-Barr virus (EBV)
HSV-8 (KSV)

Question 2

What is the structure of Herpes virus, from inside to outside?

Answer 2

Linear ds DNA core
Icosadeltahedral capsid containing capsomeres
Tegument containing VP16 and Vhs
Lipid bilayer envelope containing glycoprotein receptors

Question 3

What is the function of VP16?

Answer 3

Major transactivator protein required for initial amplification of gene expression

Question 4

What is the function of Vhs?

Answer 4

An mRNAse that mediates rapid cessation of host cell protein synthesis

Question 5

What is the life cycle of herpes simplex virus?

Answer 5

Attachment to host cell
Entry of capsid into cell
DNA deposited into nucleus
Synthesis of viral DNA and proteins
Assembly of virus components
Virus exits from cell

Question 6

How does viral cell attach to host cell?

Answer 6

Viral glycoprotein interacts with host cell surface receptors
Viral glycoprotein allows fusion of envelope to cell membrane

Question 7

What order are viral proteins synthesized in?

Answer 7

Immediate early - regulatory proteins
Early - enzymes involved in DNA synthesis
Late - structural proteins

Question 8

What protein is required for expression of immediate early protein?

Answer 8

VP16

Question 9

What makes Herpes virus able to easily replicate but also easier to target with drugs?

Answer 9

Uses its own enzymes to replicate (not the host’s)

Question 10

What are the steps of Herpes virus DNA replication?

Answer 10

Linear DNA circularizes in the cell
Early replication involves circle opening
Later replication involves strand invasion and formulation of complex nonlinear structures
Viral nuclease resolves branches, giving rise to head-to-tail concatamers
Concatamers are cleaved into individual genomes as DNA enters capsid

Question 11

How long does immunity to Herpes virus last?

Answer 11

Forever! but doesn’t prevent recurrent disease and re-infection

Question 12

What is the mode of transmission of HSV?

Answer 12

Direct contact, exposure to virus shed in secretions, olfactory transport and rarely, viremia
HSV-1: oral
HSV-2: genital

Question 13

What is the most common presentation of HSV primary infection?

Answer 13

Asymptomatic

Question 14

Who is more likely to exhibit systemic symptoms (headache, fever, malaise, and myalgia)?

Answer 14

Women, immunocompromised individuals, newborns

Question 15

Does a primary infection or recurrent infection exhibit prodromal symptoms?

Answer 15

Recurrent infection - mostly genital prodromal symptoms

Question 16

Does a primary infection or recurrent infection exhibit constitutional symptoms?

Answer 16

Primary infection

Question 17

What tissues are affected by HSV?

Answer 17

Mucous membranes
Skin
Cornea
CNS

Question 18

What type of HSV causes encephalitis in adults?

Answer 18

HSV-1

Question 19

What type of HSV causes meningitis in adults?

Answer 19

HSV-2

Question 20

How is HSV encephalitis diagnosed?

Answer 20

by PCR of HSV DNA in CSF

Question 21

Is neonatal HSV infection acquired by passage through birth canal or transplacental?

Answer 21

Passage through birth canal

Question 22

How does latent HSV develop?

Answer 22

Nucleocapsids transported to regional ganglia by retrograde axonal transport
Viral DNA is retained in sensory neurons in transcriptionally silent state, only LAT expressed
No VP16-mediated IE gene transactivation

Question 23

What site of entry determines lytic v. latent?

Answer 23

Lytic - Entry at soma

Latent - Entry at distal axons (retrograde axonal transport) caused by loss of VP16-mediated IE gene transactivation

Question 24

What is the structure of the latent viral genome?

Answer 24

Circular episome

Question 25

What is the gold standard for diagnosis of active HSV lesions?

Answer 25

Virus isolation in culture

Shell vial/Ag detection shortens duration of culture time