Herpesviruses

Question 1

Herpesviruses (general)

Answer 1

• large DNA, with icosahedral symmetry
• lineasr dsDNA, nuclear viral replication
• *hallmark of latency - either be acute or chronic from recurrent latent reactivation. T cell immune competency impt.
• Alpha: HSV-1, HSV-2, VZV
• Beta: CMV, HHV-6, HHV-7
• Gamma: EBV, KSHV, HHV-8

Question 2

Herpesviruses structure and genome

Answer 2

• dsDNA enclosed by icosahedral nuclear capsid, surrounded by tegument (granular zone) and a glycoprotetin envelope
• dsDNA, linear
• most have inverted or direct repeat sequences

Question 3

Herpesviruses replication

Answer 3

• HSV - heparan sulfate and HVEM for fusion mediation
• nucleocapsid tranport to nucleus
• transcription by 3 consecutave waves by cell DdRp
• cytoplasmic translation: immediate early-proteins - regulatory proteins, early- DNA replication, late- strucutral proteins
• replication by virus encoded DdDp via “rolling cirlce”
• nucleocapsid assembly in nucelus, enveloped trasniently by nuclear membrane budding
• nucleocapsid bud intp ER, mature, then secretory pathway causing lysis

Question 4

HSV-1, HSV-2 (alpha)

Answer 4

Key:

• HSV-1 (oral/respiratory excretions). HSV-2 (sexual, congenital)
• HSV-1: acute gingivostomatitis, cold sores, corneal scarring, skin lesions, *adult temporal encephalitis-sequalae
• HSV-2: genital painful vesicular lesions, aspetic meningitis-NO sequelae, neonate encephalitis, CNS, visceral infection- hematogenous dissemination
• acyclovir - prevents viral DNA synthesis
• no vaccine

Extra:

• attaches and enter nerve endings -> retrograde axonal transport to sensry ganglia -> neuron lysis or latent infection -> stress reactivation -> virus anterograde axonal transport to epithelium -> replication -> asymptomatic or vesicular lesions (virus shedding)
• cell mediated needed for resolutoin

Question 5

VZV

Answer 5

Key:

• Varicella - children:
• primary varicella rash (chicken pox) inferior progression of lesions which transform asynchronously
• respiratory or vesicular fluid transmission, infectious until lessions crust
• potential bacterial infection: S. pyogens - Group A (necrotizing fasciitis, pyomyositis)
• Zoster - :
• painful dermatomal vesicular eruptions - trunk & head
• most severe -> neuralgia
• VZV live vaccine & VZV immunoglobulin passive immunization
• acyclovir

Extra:

• upper respiratory infection and local replication -> primary viremia -> reticuloendothelial replication -> secondary viremia -> cutaneous lesions (chicken pox) -> latent sensory ganglia -> reactivated shingles
• Hodgkin disease predisposing

Question 6

CMV

Answer 6

Key:

• transmission: salivary, parenterally, sex
• mostly subclinical
• congenital - most common, *severe learning disabilities, jaundice, anemia, can shed for many years
• self-limited mild mononucleosis - fever, hepatitis, splenomagaly, >50% mononuclear humor
• *common allograft loss
• tx: immunoglobulin, antivirals

Extra:

• leukocyte latency
• AIDS retinits, esophagitis, colitis
  *

Question 7

EBV

Answer 7

Key:

• infectious mononucleosis (febrile) young adults / asymptomatic children - exudative pharyngitis, vervical lymphadenopathy, depatosplenomegaly
• immortalizes infected B cells-hyperammaglobulinemia
• AIDS/transpolants tumors
• Cyclosporin A (inhibit T cell / NK fx) for transplants -> EBV neoplasms
• Africa - Burkitt lymphoma - lymphadenopathy neck/head
• Chinese - nasophoryngeal carcinoma

Extra:

• salava -> oropharynx replication and lysis -> B cell latency (C3d target) -> B cell immortality -> transient hyperhammaglbulinemia (IgM)
• NK, T cell attack
• salivary transmission
• no vaccine, immune prophylaxis
• antivirals not very effective