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Flashcards in Neurotropic Viruses Deck (25):
1

What do Herpesvirus look like?

  • 180-200nm in diameter
  • Large genome: 100-250 kbp
  • Enveloped viruses are labile in the environment: infectious virions survive up to 2 hours on skin, up to 4 hours on plastic surfaces

2

What are the α herpesviruses?

What are the ß herpesviruses?

What are the γ herpesviruses?

What are the α herpesviruses?

  • Hepes simplex virus (HSV-1, HSV-2)
  • Varicella zoster virus
  • HHV-1, HHV-2, HHV-3

What are the ß herpesviruses?

  • Cytomegalovirus (CMV)
  • Roseolovirus (HHV-6)
  • HHV-7, HHV-5, HHV-6A, - 6B

What are the γ herpesviruses?

  • Epstein-Barr Virus (EBV)
  • Kaposi's Sarcoma Virus (KSHV)
  • HHV-4
  • HHV-8

3

Characteristics of α herpesviruses

  • Short replication cycle
  • Latency primary in sensory ganglia (neurons)
  • Broader host range

4

Defining biological properties of a herpesvirus

  • Encode a collection of enzymes involved in nucleotide metabolism, DNA synthesis, protein kinase
  • Synthesis of viral DNA and capsid assembly in the nucleus
  • Rest of virion put together in cytoplasm
  • Two life cycles: lytic replication and latency

5

Latent infection

  • Circular viral DNA is associated with host nucleosomes and is maintained as an episome
  • Very little if any viral gene expression - repressed through viral chromatin-associated histone code
  • Poorly defined mechanisms trigger reactivation
    • Immune system
    • UV radiation
    • Physical trauma

6

Herpesvirus last ______

Forever

Maintain latency with occaisonal reactivation for the life of the host

7

Transmission:

  • Person to person
  • Intrauterine
  • Perinatal
  • Skin-skin
  • genital-genital
  • Oral-Genital
  • Oral-Oral

8

HSV reservoir:

______ is more commonly shed from oral cavity

______ is more commonly shed from genital tract

Humans are the only reservoir

HSV-1; HSV-2

9

HSV pathogenisis

  1. VIral transmission to mucosa (epithelium)
  2. Robust lytic replication (primary infection)
  3. Virus infects sensory neurons - retrograde transport to the sensory ganglia - latency
  4. Latency characterized by expression of group of viral mRNAs called Latency Associated Transcripts (LAT's) - never translated into protein - repress HSV gene expression
  5. Unknown stimuli trigger viral reactivation - viral capsids subjected to anterograde transport with mature virions

10

Sites of latency

HSV-1:

HSV-2:

HSV-1: trigeminal ganglia

HSV-2: sacral ganglia

11

Frequency of reactivation

In untreated HSV-2 positive individuals, the chance of subclinical reactivation at a genital site is approximately 25% on any given day

12

Exogenous reinfection

Reinfection of a seropositive individual with a different strain of HSV (possible but uncommon)

13

Treatment of herpesviruses

  • Current treatment approaches targeting replicating virus ONLY
  • No treatments available that would clear latent herpesvirus infection
  • Acyclovir - treatment of choice
  • No vaccines for HSV (varicella zoster virus only herpes vaccine)

14

How does Acyclovir work

Competes with dGTP for viral DNA polymerase

Polymerase binds to ACV-PPP irreversibly

Ties up polymerase

A image thumb
15

HSV-1 and HSV-2 Primary vs. Recurrent mucocutaneous infections

  • Genital disease (both HSV-1 and HSV-2) - treatment reduces shedding by 60-80%)
  • Primary oral-facial infection (HSV-1 most common) - Herpes gingivostomatitis or pharyngitis
  • Recurrent oral-facial infection - herpes labialis

16

HSV-1 and 2: Neonatal herpes:

  • Inoculation during birth (most common)
  • Inoculation during pregnancy results in multiple birth defects
  • Disseminated replication
  • CNS is commonly affected
  • Disease usually manifests within days of life - may not have skin lesions
  • Mortality is high, even if treated with acyclovir
  • Neurological abnormalities in survivors

 

17

Herpes keratitis and conjunctivitis:

Herpes gladiatorium:

Herpes whitlow:

Herpes keratitis and conjunctivitis: leading cause of blindness in the US

Herpes gladiatorium: Dermatitis of athletes in contact sports

Herpes whitlow: Handdermatitis - significant problem in health care workers - gloves do not prevent transmission

18

HSV-1 and 2 diagnosis

  • Vesicles at the site of inoculation
  • Clinical virology lab: culture of virus immunofluorescence using antibodies against HSV antigens, PCR assays
  • Serology to determine infection status

19

Varicella Zoster: epidemiology and transmission

  • Humans only reservoir
  • Cuasative agent of chickenpox
  • Spread through person to person contact
  • Virus is aerosolized both from lesions and respiratory tract
  • Can also be transmitted via direct contact with the skin lesions

20

Varizella Zoster: Course of Disease

  • Virus replication in T cells, epithelial and endothelial cells
  • Latency is maintained in sensory nerve ganglia - many ganglia are involved
  • Several viral gene products are actively transcribed and translated within latently infected neurons (unlike HSV) - unknown how virus deals with immune recognition
  • Primary infection may involve CNS

21

Chickenpox (characteristics)

  • Primary infection with VZV
  • Blisters, itching, malaise, fever
  • Aspirin counterindicated - Reye's syndrome
  • Serious complications (skin infection, pneumonia) more common in adulthood
  • Neonatal VZV is extremely rare
  • Can lead to fatality in immunocompromised patients
  • Treatment includes antivirals, such as acyclovir, VZV immune globulin

22

Herpes Zoster

  • Reactivation of latent VZV from a single sensory ganglia (most cases)
  • 1 million cases/year in US (usually > 50 years old)
  • In Trigeminal ganglia can lead to vision impairment
  •  

23

Postherpetic neuralgia

A significant complication of zoster: severe pain without vesicular lesion, can mimic appendicitis or a heart attack. Pain can last for many months. Antivirals have no effect

24

Varicella Zoster: Diagnosis

  • Differential diagnosis must exclude bacterial or enterovirus infections
  • Most important diferential was smallpox historically
  • Clinical lab diagnosis: VZV DNA PCR, detection of VZV antigens in lesions by immunofluorexcence
  • Serology to determine immune status of individual

25

VZV vaccine

Live attenuated virus - Oka strain (1995)

  • Up to 15-20% of vaccinated individuals get infected with wild type VZV that goes on to establish latency
  • Reduces severity of primary infection
  • Establishes lifelong latent infection
  • Can be transmitted to immunocompromised
  • Immunity in aged not as long lasting; rcommended in population > 60 years of age