TY - JOUR T1 - Environmental nanoparticle exposure triggers gammaherpesvirus reactivation via the MAPK signaling pathway in macrophages JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2022.4576 VL - 60 IS - suppl 66 SP - 4576 AU - L Han AU - V Haefner AU - D Kutschke AU - B Steer AU - A Fuchs AU - M Irmler AU - J Beckers AU - A Feuchtinger AU - M Heier AU - A Peters AU - H Adler AU - T Stoeger Y1 - 2022/09/04 UR - http://erj.ersjournals.com/content/60/suppl_66/4576.abstract N2 - Environmental particle inhalation and persistent herpesvirus infection are omnipresent and associated with chronic lung diseases. Previously, we showed that pulmonary exposure to soot-like carbonaceous nanoparticles (CNP) or fiber-shaped engineered double walled carbon nanotubes (DWCNT) induced lytic viral protein expression increase in latently murine gammaherpesvirus-68 (MHV-68) infected mouse lungs, with similar pattern as acute infection suggesting virus reactivation. However, the association between particle exposure and human herpesvirus reactivation and the underlying mechanisms remain unclear.In the KORA cohort study, we found Human Herpesvirus 6 (HHV6) antibody titers are associated with high particle number concentration (PNC). In MHV-68 infected murine model, CNP exposure reactivated herpesvirus mainly localized to CD11b+ infiltrating macrophages. Mechanistically, ERK1/2, JNK and p38 were rapidly activated within the first hour after NPs exposure in persistently MHV-68 infected bone marrow derived macrophages (Ana-1/MHV-68), followed by lytic viral gene expression upregulation and viral titer increase. Further, pharmacological inhibition of p38 activation abrogated CNP but not DWCNT triggered virus reactivation. In vivo, p38 inhibitor pretreatment in latently infected mice attenuates MHV-68 reactivation induced by CNP exposure.Our findings suggest that environmental particle exposure triggers herpesvirus reactivation in the lung via p38 MAPK dependent signaling, and pharmacological inhibition of p38 might alleviate ambient particle exposure related disease exacerbations.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4576.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -