Leucine-rich repeat (in Flightless I) interacting protein-1 regulates a rapid
type I interferon response
#MMPMID20586614
Bagashev A
; Fitzgerald MC
; Larosa DF
; Rose PP
; Cherry S
; Johnson AC
; Sullivan KE
J Interferon Cytokine Res
2010[Nov]; 30
(11
): 843-52
PMID20586614
show ga
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 NF?B 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.
|Animals
[MESH]
|Endosomes/virology
[MESH]
|Influenza A virus/*immunology/pathogenicity
[MESH]
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