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Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):E176-85. doi: 10.1073/pnas.1412984112. Epub 2014 Dec 29.

Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota.

Author information

1
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.
2
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;
3
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, United Kingdom;
4
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;
5
Drosophila Genetics and Epigenetics, Université Pierre et Marie Curie Paris VI, CNRS UMR 7622-Biologie du Développement, 75252 Paris, France; and.
6
Laboratory of Arbovirus and Insect Vectors, Department of Virology Institut Pasteur, 75724 Paris, Cedex 15, France;
7
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.

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.

KEYWORDS:

arbovirus; host–pathogen interactions; innate immunity; insect immunity; malaria

PMID:
25548172
PMCID:
PMC4299212
DOI:
10.1073/pnas.1412984112
[Indexed for MEDLINE]
Free PMC Article

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