Seoul virus suppresses NF-kappaB-mediated inflammatory responses of antigen presenting cells from Norway rats.
Hantavirus infection reduces antiviral defenses, increases regulatory responses, and causes persistent infection in rodent hosts. To address whether hantaviruses alter the maturation and functional activity of antigen presenting cells (APCs), rat bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) were generated and infected with Seoul virus (SEOV) or stimulated with TLR ligands. SEOV infected both DCs and macrophages, but copies of viral RNA, viral antigen, and infectious virus titers were higher in macrophages. The expression of MHCII and CD80, production of IL-6, IL-10, and TNF-alpha, and expression of Ifnbeta were attenuated in SEOV-infected APCs. Stimulation of APCs with poly I:C prior to SEOV infection increased the expression of activation markers and production of inflammatory cytokines and suppressed SEOV replication. Infection of APCs with SEOV suppressed LPS-induced activation and innate immune responses. Hantaviruses reduce the innate immune response potential of APCs derived from a natural host, which may influence persistence of these zoonotic viruses in the environment.
Au
Rebecca Y
RY
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Jedlicka
Anne E
AE
Li
Wei
W
Pekosz
Andrew
A
Klein
Sabra L
SL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D018778:Hantavirus Infections / Q000209:etiology / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007249:Inflammation / Q000517:prevention & control; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D029263:Seoul virus / Q000472:pathogenicity* / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D014779:Virus Replication
D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D011070:Poly I-C