HSV and EBV Infections: Seropositivity, Neuronal Involvement, and Reactivation, Slides of Human Resource Management

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HSV Infections

• Population is >80% seropositive

• ~2.5 X 10^8 in U.S. have latent virus

• 4 X 10^7 will experience recurrence

! - some asymptomatic shedding

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HSV Infection of Ganglia

Both sensory and sympathetic ganglia can be infected

What Do LATs Do?

• LAT-^ virus reactivates poorly

• 2 ORFs are contained in the LAT sequence but no

know protein has been associated with them

• Encode MIRs that could inhibit expression of

! - ICP0, a potent transcriptional activator ! - γ34.5 a neurovirulence gene that activates PPIa 26

Why Neurons?

• Neurons don’t replicate or divide, genome is

established and readily persists

• Insensitive to antivirals and immune surveillance

! - blood brain barrier

• But.......how do they survive the 1˚ infection?

• Why are there multiple copies of virus DNA?

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Reactivation Triggers

• What flips the switch?

• Stress

• Glucocorticoids

• In a model system exogenous ICP0 can reactivate

• The VP16 conundrum

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Establishment, Maintenance &

Reactivation

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EBV a γ Herpesvirus

• 95% of adults are seropositive and carry the genome

• Virus resides in persistently infected non-proliferating

memory B lymphocytes

• Causal agent of:

! - Hodgkins lymphoma ! - Infectious mononucleosis ! - Nasopharyngeal carcinoma ! - Burkitt’s lymphoma

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EBV Lifecycles

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Latently infected B cell (^) Persistently infected B cell