Reactivation of latent virus infection links air pollutants to chronic lung disease

Particulate air pollution and gammaherpesviruses are omnipresent in human society. These viruses persist lifelong in the host in a latent state, and switch to a lytic phase upon reactivation. We have previously shown, that pulmonary exposure to carbon nanoparticles (CNPs), a typical component of urban air pollution, and engineered carbon nanotubes (CNTs) can lead to the reactivation of latent murine gammaherpesvirus 68 (MHV-68) in the lungs of mice. Repetitive CNP and CNT inhalation scenarios might contribute to the exacerbation of chronic lung diseases (CLD) like COPD and pulmonary fibrosis. Here we test whether a repeated CNP exposure triggers additive pulmonary inflammatory effects in the mouse model of MHV-68 reactivation and thereby might contribute to exacerbations of CLDs. Repeated intratracheal dosing of latently MHV-68 infected mice with 50µg CNPs at a time interval of 55 days caused increased and prolonged airspace lymphocyte numbers in MHV-68 infected and CNP treated mice, not observed either in animals infected or CNP treated only. The lymphocyte infiltration was accompanied by increased levels of pulmonary Tnf, Saa3 and Spp1 gene expression, elevated BAL protein and IgM levels and mean cord length, all together indicating progressive emphysema like alveolar barrier damage. Lung damage furthermore was associated with high serum SAA3 concentrations suggesting systemic inflammation. These observations suggest that repeated CNP exposure of latently MHV-68 infected lungs leads to a prolonged inflammatory response with alveolar-capillary barrier disruption and potential systemic consequences, which may contribute to the exacerbation of CLDs or related comorbidities like cardiovascular disease.