Polymorphism analyses and protein modelling inform on functional specialization of Piwi clade genes in the arboviral vector Aedes albopictus

Michele Marconcini (1) , Luis Hernandez (1) , Giuseppe Iovino (1) , Vincent Houé (2) , Federica Valerio (1) , Umberto Palatini (1) , Elisa Pischedda (1) , Jacob E Crawford (3) , Bradley J White (3) , Teresa Lin (3) , Rebeca Carballar-Lejarazu (1) , Lino Ometto (1) , Federico Forneris (1) , Anna-Bella Failloux (2) , Mariangela Bonizzoni (1)

1 DBB UNIPV - Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani" = Department of Biology and Biotechnology [Univ di Pavia]
2 Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors
3 Verily Life Sciences Inc

Current knowledge of the piRNA pathway is based mainly on studies on Drosophila melanoga-ster where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as dengue and chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma and cross-talk with proteins of recognized antiviral function cannot be excluded for some Piwi proteins. These observations underscore the importance of expanding our knowledge of the piRNA pathway beyond the model organism D. melanogaster. Here we focus on the emerging arboviral vector Aedes albopictus and we couple traditional approaches of expression and adaptive evolution analyses with most current computational predictions of protein structure to study evolutionary divergence among Piwi clade proteins. Superposition of protein homology models indicate possible high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with several sites under positive selection. Analysis of the expression profiles of Piwi transcripts during mosquito development and following infection with dengue serotype 1 or chikungunya viruses showed a concerted elicitation of all Piwi transcripts during viral dissemination of dengue viruses while maintenance of infection relied on expression of primarily Piwi5. Opposite, establishment of persistent infection by chikungunya virus is accompanied by increased expression of all Piwi genes, particularly Piwi4 and, again, Piwi5. Overall these results are consistent with functional specialization and a general antiviral role for Piwi5. Experimental evidences of sites under positive selection in Piwi1/3, Piwi4 and Piwi6, that have complex expression profiles, provide useful knowledge to design tailored functional experiments.

Mots clés: Viral gene expression; Drosophila melanogaster; Mosquitoes; Chikungunya virus; Ovaries; Chikungunya infection; Sequence alignment; Small interfering RNAs

Domaines: Virologie

Michele Marconcini, Luis Hernandez, Giuseppe Iovino, Vincent Houé, Federica Valerio, et al.. Polymorphism analyses and protein modelling inform on functional specialization of Piwi clade genes in the arboviral vector Aedes albopictus. PLoS Neglected Tropical Diseases, 2019, 13 (12), pp.e0007919. ⟨10.1371/journal.pntd.0007919⟩. ⟨pasteur-02434641⟩