Effects of Chronic Diurnal Disruption and Acute Inflammatory Challenge on Mice with Latent Murine Gammaherpesvirus Infection.

Observed Findings

• IFNgKO mice had consistently higher lytic viral levels and more frequent viral replication than BALB/cByJ mice during the 6-week acute phase
• Mice exposed to shift-work-mimicking light cycles followed by LPS injection during latency showed greater viral loads and more replicating virus in lung tissue at 7 days post-injection
• Cytokine and chemokine concentrations changed at 1 day post-LPS but returned toward baseline by 7 days
• Circadian disruption alone did not consistently alter acute viral measures
• The combination of chronic diurnal disruption AND acute inflammatory challenge produced the most pronounced viral reactivation

Inferred Conclusions

• Chronic circadian disruption combined with acute inflammatory challenge during latent viral infection enhances viral reactivation, particularly in immunocompromised hosts
• Impaired interferon-gamma signaling increases susceptibility to both acute and latent gammaherpesvirus infection
• The enhanced viral reactivation and associated cytokine responses may contribute to 'sickness behavior' symptoms resembling infectious disease and potentially chronic fatigue syndrome
• Timing and context of immune challenges during periods of circadian misalignment may be critical in determining disease severity

Remaining Questions