Seoul virus alters proinflammatory and antiviral responses of macrophages from Norway rats (45.14)

Abstract

Abstract Hantaviruses cause persistent infection, upregulation of regulatory responses, and downregulation of proinflammatory responses in reservoir hosts. To determine whether hantaviruses suppress the inflammatory activity of antigen presenting cells, we infected bone marrow-derived macrophages (BMDMs) from Norway rats with Seoul virus (SEOV). The expression of MHCII and CD80, production of IL-6, IL-10, and TNF-α, and expression of Ifnβ were attenuated after infection. Stimulation of BMDMs with poly I:C prior to SEOV infection increased the expression of activation markers and production of inflammatory cytokines and suppressed SEOV replication. Infection with SEOV also suppressed LPS-induced activation of BMDMs, including NF-κB signaling and production of proinflammatory cytokines. Because inhalation is a major route of hantavirus transmission between rodents, with alveolar macrophages providing the first line of defense against inhaled pathogens and playing a pivotal role in the initiation of infection-induced inflammatory response, we are currently investigating whether rat alveolar macrophages response to SEOV infection in a similar manner as BMDMs and whether SEOV infection of alveolar macrophages enhances regulatory responses, including TGF-β production. Hantavirus-induced inhibition of inflammatory responses of macrophages may be one mechanism contributing to the persistence of virus in reservoir hosts.