Viral Skin Infections

Question 1

General Structure & Classification

Answer 1

• 150-200 nm
• Linear ds DNA 150-200 kbp
• icosahedral capsid w/ 162 capsomere
• Infect mucosal epithelial cells
• Replicate in nucleus
• Alpha herpesvirus: HSV1 HSV1 VZV

Question 2

Herpes Simplex

Answer 2

HSV1: labial lesions (Cold sores), fever blisters, keratitis, encephalitis

• HSV2: Genetial lesions severe CNS disease in neonates
• transmitted by close contact/sex

Question 3

Herpes Zoster (VZV)

Answer 3

• chicken pox and shingles

- transmitted thru respiratory droplets

Question 4

Herpesvirus Life Cycle

Answer 4

• Lytic replication: in epithelial cells takes over cell replication
  
  • macromolecular synthesis & virus assembly
  • Cell death
• 4 gene expression phases: immediate early, early, DNA replication, & late
• Latency: circular viral genome maintained in neurons w/o replication
  
  • Express LAT transcript
• Reactivation: limited viral replication in neurons w/ transport of viral capsid to axonal terminals
  
  • egress to regions innervated by neurons

Question 5

HSV enzymes used in DNA Replication

Answer 5

• Ribonucleotide reductase
• thimidine kinase
• primase/helicase
• DNA polymerase

Question 6

HSV latency & Reactivation

Answer 6

• HSV1 latency: episomal DNA in trigeminal ganglia
  
  • latency associated transcript (LAT)
  • Evade immune detection
• HSV Reactivation: stress, sun, trauma, menstruation, infection, immune impaired
• HSV2 Reactivation often asymptomatic
• VSV reactivation: immune suppressed
  
  • Old age

Question 7

Clinical Features of HSV (4)

Answer 7

• Primary infection: systemic symptoms like fever/malaise
• Reactivation: Prodromal symptoms- pain, numbness, itchiness, tingling
• Acute infection: tissue destruction or immunopathologic response
  
  • Vesicles on erythematous base
  • grouped at single site
• Subclinical viral shedding: key to transmission and risk to neonates

Question 8

Immune Response to HSV Infection

Answer 8

• Antibodies have MINOR role
• Cell mediated mechanisms most important
• AIDS pts, transplant pts, chemo pts, etc susceptible to reactivation & prolonged infection due to decreased cell mediated immunity

Question 9

Varicella Zoster Virus (VZV)

Answer 9

• Varicells: chicken pox
• Zoster: shingles
• Vaccination

Question 10

Herpes Thymidine Kinase Inhibitors

Answer 10

• Acyclovir or ganciclovir
• Analogs of Guanosine- incorporated into viral DNA
• DNA chain terminator activated by viral TK
• Incorporation into viral DNA terminates replication
• Valacyclovir is prodrug converted to acyclovir
  
  • Better bioavailability for HSV & VZV

Question 11

Herpes DNA polymerase Inhibitors

Answer 11

• Phosphonoacetic acid
• Phosphonoformate (toscarnet)
• Pyrophosphate analogs: bind directly to PP-binding sites
• Req continious IV pump
• Tx CMV in AIDS pts
• Renal side effects