title: Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota.
abstract: Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o'nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens.
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France; Graduate School of Life Sciences ED515, Sorbonne Universités UPMC Paris VI, 75252 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Carissimo
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France; MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, United Kingdom;
authors.forename: Emilie
authors.initials: E
authors.lastname: Pondeville
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, United Kingdom;
authors.forename: Melanie
authors.initials: M
authors.lastname: McFarlane
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, United Kingdom;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dietrich
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France;
authors.forename: Christian
authors.initials: C
authors.lastname: Mitri
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.affiliation: Drosophila Genetics and Epigenetics, Université Pierre et Marie Curie Paris VI, CNRS UMR 7622-Biologie du Développement, 75252 Paris, France; and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Antoniewski
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Bourgouin
authors.affiliation: Laboratory of Arbovirus and Insect Vectors, Department of Virology Institut Pasteur, 75724 Paris, Cedex 15, France;
authors.forename: Anna-Bella
authors.initials: AB
authors.lastname: Failloux
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, United Kingdom;
authors.forename: Alain
authors.initials: A
authors.lastname: Kohl
authors.affiliation: Unit of Genetics and Genomics of Insect Vectors, Department of Parasites and Insect Vectors and CNRS Unit of Hosts, Vectors, and Pathogens, Unité de Recherche Associée 3012, Paris, France; Department of Microbiology, University of Minnesota, Minneapolis, MN 55108; kvernick@pasteur.fr.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Vernick
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000635:transmission; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D001102:Arbovirus Infections / Q000276:immunology / Q000635:transmission; D001103:Arboviruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D004064:Digestive System / Q000276:immunology / Q000382:microbiology / Q000821:virology; D005260:Female; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007303:Insect Vectors / Q000235:genetics / Q000276:immunology / Q000821:virology; D053612:Janus Kinases / Q000276:immunology; D064307:Microbiota; D064202:O'nyong-nyong Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D034741:RNA, Small Interfering; D050791:STAT Transcription Factors; D053612:Janus Kinases
keywords: arbovirus; host–pathogen interactions; innate immunity; insect immunity; malaria