TY - JOUR
T1 - ERK signaling couples nutrient status to antiviral defense in the insect gut
AU - Xu, Jie
AU - Hopkins, Kaycie
AU - Sabin, Leah
AU - Yasunaga, Ari
AU - Subramanian, Harry
AU - Lamborn, Ian
AU - Gordesky-Gold, Beth
AU - Cherry, Sara
PY - 2013/9/10
Y1 - 2013/9/10
N2 - A unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. We show that the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines, providing insight into the molecular determinants of the antiviral "midgut barrier." Wild-type flies are refractory to oral infection by arboviruses, including Sindbis virus and vesicular stomatitis virus, but this innate restriction can be overcome chemically by oral administration of an ERK pathway inhibitor or genetically via the specific loss of ERK in Drosophila intestinal epithelial cells. In addition, we found that vertebrate insulin, which activates ERK in the mosquito gut during a blood meal, restricts viral infection in Drosophila cells and against viral invasion of the insect gut epithelium. We find that ERK's antiviral signaling activity is likely conserved in Aedes mosquitoes, because genetic or pharmacologic manipulation of the ERK pathway affects viral infection ofmosquito cells. These studies demonstrate that ERK signaling has a broadly antiviral role in insects and suggest that insects take advantage of cross-species signals in the meal to trigger antiviral immunity.
AB - A unique facet of arthropod-borne virus (arbovirus) infection is that the pathogens are orally acquired by an insect vector during the taking of a blood meal, which directly links nutrient acquisition and pathogen challenge. We show that the nutrient responsive ERK pathway is both induced by and restricts disparate arboviruses in Drosophila intestines, providing insight into the molecular determinants of the antiviral "midgut barrier." Wild-type flies are refractory to oral infection by arboviruses, including Sindbis virus and vesicular stomatitis virus, but this innate restriction can be overcome chemically by oral administration of an ERK pathway inhibitor or genetically via the specific loss of ERK in Drosophila intestinal epithelial cells. In addition, we found that vertebrate insulin, which activates ERK in the mosquito gut during a blood meal, restricts viral infection in Drosophila cells and against viral invasion of the insect gut epithelium. We find that ERK's antiviral signaling activity is likely conserved in Aedes mosquitoes, because genetic or pharmacologic manipulation of the ERK pathway affects viral infection ofmosquito cells. These studies demonstrate that ERK signaling has a broadly antiviral role in insects and suggest that insects take advantage of cross-species signals in the meal to trigger antiviral immunity.
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U2 - 10.1073/pnas.1303193110
DO - 10.1073/pnas.1303193110
M3 - Article
C2 - 23980175
AN - SCOPUS:84883794126
SN - 0027-8424
VL - 110
SP - 15025
EP - 15030
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 37
ER -