Social stress and the reactivation of latent herpes simplex virus

type 1

Authors: David A. Padgett, John F. Sheridan, Julianne dorne, Gary G. Berntson, Jessica Candelora and

Ronald Glaser

By: Shauna Halaharvi

What it’s all about…….ooo yeah!!

• Nervous, endocrine and immune systems communicate through biochemical language: ligands

• Looking at the effects on the pathophysiology of infectious agents.– Influenza virus– Herpes simplex virus type 1 (HSV-1)– Mycobacterium tuberculosis

• These systems are influenced by stress which might cause sickness.

Cont..

• Schmidt et al showed traumatic life experiences were common with people with frequent oral HSV

• Immune suppression and stress could cause break outs.

Previous work

• Relationship b/w stress-induced immune modulation, innate immunity, and the virus-specific T cell response to HSV-1

• How stress impacts virus specific memory immune response

• RST mice went downhill for natural killer cell lysis and also in virus-specific cytotoxic T lymphocytes to HSV-1

What now??

• The development of a model to study the impact of psychological and social stress on the recrudescence of HSV-1.

Methods: Mice and Virus Infection

• Hsv-1 antibody-negative BALB/c male mice at 4-6 wks.

• 12 hour days and nights

• Right cornea scarified

• Swabbed eyes with type -1 Dacron swabs

• Left for 5 weeks

Methods: UV Sources and Irradiation Procedure

• Anesthetized as previously discussed

• A shield with eye hole

• UV dosage of 250-260 mJ/ cm

Methods: RST and Stress Paradigm

• Restraint stressed

• Ventilated 50-ml centrifuge tubes

• Control mice– No food– No water

Methods: Social Reorganization Paradigm

• Aggressor males

• Observe for 15 min . 3X15 min periods with random intervals during a 3-hr period

• Noticed aggressive and defensive behavior

Results: The Influence of RST Stress on HSV-1 Reactivation

• 16 males 5-6 weeks old• All mice showed evidence

of being infected with HSV-1

• None of them showed evidence of spontaneous reactivation of latent HSV-1

• 8 days of 16 hr cycle of RST stress-HPA

Cont…

• After 6 cycles of RST – corticosterone levels increased 5 fold (222.9 +- 29.8 ng/ ml) to control (48.8 +- 7.3 ng/ml) Fig 1.

• 7 of 16 in UV group in exp 1. and 5 of 10 in exp 2 (total 46.2 %) showed reactivation of latent HSV-1

• The use of RST did not increase reactivation within UV-irradiated group

Results: The Effect of a Social Stressor on the Reactivation of

HSV-1

Results: Social Dominance and HSV-1 Reactivation

• 3 forms observed– Offensive, defensive, and

submissive

• If social environment and behavioral interactions –the ones with the more amount of interactions and severe will be influenced.

• Dominant mouse is more likely to show signs of HSV-1

Findings

• Exposure of eyes-reactivation of latent HSV-1• Mice with hierarchy disruption- reactivation of

latent HSV-1• Stress has ability to modulate the reactivation/

replication • Corticosterone itself is insufficient to reactivate

latent HSV-1 as the high levels of serum corticosterone induced by RST stress did not lead to viral shedding.

Future Research

• The mechanisms underlying the interactions among products of the nervous, endocrine, and immune system.

• Social stress to model-explore complex relationships among behavior, stress-associated immune modulation…