Particle Inhalation Triggered Reactivation of Latent Virus Infections - A New Link Between Air Pollution and the Development of Chronic Lung Disease?
Lianyong Han, Verena Haefner, Ali Oender Yildirim, Annette Peters, Heiko Adler, TOBIAS STOEGER,
Helmholtz Zentrum München, Germany Abstract Number: 116
Working Group: Carbonaceous Aerosol
AbstractBackground: Particulate air pollution and gammaherpesviruses are omnipresent in urban life, with basically all the global population breathing air exceeding WHO guideline limits and almost every adult infected by at least one herpesvirus type. Upon infection, herpesviruses persist lifelong in the host in a latent state, switching to the lytic, replicative phase only following reactivation. We have previously shown that pulmonary exposure to soot-like carbon nanoparticles (CNPs), a typical component of urban air pollution, can lead to reactivation of latent Murine gammaherpesvirus-68 (MHV-68) in the lungs of mice accompanied by an inflammatory response.
Hypothesis: We hypothesize that boosting the production of lytic proteins with subsequent immunomodulation by repetitive particle exposure scenarios contributes to development of chronic lung diseases.
Results: In a population-based study, using the German KORA FF4 cohort (2778 participants, 38 to 88 years), we detected an association between high particle number concentration and elevated Human herpesvirus 6 antibody serum titers, pointing to the human relevance of particle triggered virus reactivation. Twice repeated pulmonary dosing of MHV-68 infected mice with 50µg CNP, at an interval of 55 days, caused increased and prolonged lymphocyte accumulation in the airspace of MHV-68 infected and particle treated mice, not observed in animals infected or particle treated only. The over one week after the last exposure rising lymphocyte infiltration was accompanied by elevated inflammation and alveolar-damage markers, as well as histological changes indicating a progressive emphysema like pathology. Mechanistic investigations in MHV-68 infected macrophages uncovered by CNP exposure triggered p38 MAP-Kinase signaling as dominant driver of virus reactivation, and pretreatment with a pharmacological p38-inhibitor diminished CNP-induced virus reactivation in infected mice.
Conclusions: Together, our observations suggest that latent gammaherpesvirus infection of our lungs might pose a new pathway of susceptibility to air pollutants with inhibition of p38 as a preventive therapeutic target.