Social stress and the reactivation of latent herpes simplex virus type 1

1. 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

2. 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. 

3. Cont.. • Schmidt et al showed traumatic life experiences were common with people with frequent oral HSV • Immune suppression and stress could cause break outs.

4. 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

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

6. 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

7. Methods: UV Sources and Irradiation Procedure • Anesthetized as previously discussed • A shield with eye hole • UV dosage of 250-260 mJ/ cm

8. Methods: RST and Stress Paradigm • Restraint stressed • Ventilated 50-ml centrifuge tubes • Control mice • No food • No water

9. 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

10. 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

11. 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

12. Results: The Effect of a Social Stressor on the Reactivation of HSV-1

13. 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

14. 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.

15. 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…