Leucine-rich repeat (in Flightless I) interacting protein-1 regulates a rapid type I interferon response.
The cell autonomous response to viral infection is carefully regulated to induce type I interferons (IFNs), which in turn induce the establishment of an antiviral state. Leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) and LRRFIP2 are 2 related proteins that have been identified as interacting with MyD88 and Flightless I homolog, a leucine-rich repeat protein. LRRFIP2 positively regulates NFκB and macrophage cytokine production after lipopolysaccharide, but less is known about LRRFIP1. We hypothesized that LRRFIP1 could be more important in antiviral responses, as overexpression led to type I IFN production in a pilot study. The induction of type I IFNs occurred even in the absence of virus, but was enhanced by the presence of virus. Conversely, knockdown of LRRFIP1 compromised IFN expression. We found that LRRFIP1 was rapidly recruited to influenza-containing early endosomes in a p38-dependent fashion. This was specific for virus-containing endosomes as there was almost no colocalization of LRRFIP1 with early endosomes in the absence of virus. Further, LRRFIP1 was recruited to RNA-containing vesicles. Taken together, these data suggest that LRRFIP1 participates in cell responses to virus at early time points and is important for type I IFN induction.
Bagashev
Asen
A
The Division of Allergy Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Fitzgerald
Michael C
MC
Larosa
David F
DF
Rose
Patrick P
PP
Cherry
Sara
S
Johnson
Alfred C
AC
Sullivan
Kathleen E
KE
D000818:Animals; D011992:Endosomes / Q000821:virology; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D019076:Transgenes / Q000235:genetics
D007370:Interferon Type I; C558582:Lrrfip1 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins