Immune-suppression by OsHV-1 viral infection causes fatal bacteraemia in Pacific oysters

De Lorgeril J ,Lionel Dégremont ,Marianne Alunno‐Bruscia ,Aude Lucasson ,Bruno Petton ,Jeremie Vidal‐Dupiol ,Leroy Ma ,Nicole Faury ,Agnès Vergnes ,Philippe Haffner ,Richard Galinier ,Camille Clérissi ,Benjamín Morga ,Le Roux F ,Jean-Michel Escoubas ,Marlène Chiarello ,Cristian Chaparro ,Tristan Rubio ,D Régler ,Ève Toulza ,Yannick Gueguen ,Caroline Montagnani ,Adeline Perignon ,Pierre Boudry ,Guillaume M Charrière ,Delphine Destoumieux-Garzón ,M Lafont ,Anne-Marie Delort ,Guillaume Mitta

doi:10.1038/s41467-018-06659-3

Abstract

Infectious diseases are mostly explored using reductionist approaches despite repeated evidence showing them to be strongly influenced by numerous interacting host and environmental factors. Many diseases with a complex aetiology therefore remain misunderstood. By developing a holistic approach to tackle the complexity of interactions, we decipher the complex intra-host interactions underlying Pacific oyster mortality syndrome affecting juveniles of Crassostrea gigas, the main oyster species exploited worldwide. Using experimental infections reproducing the natural route of infection and combining thorough molecular analyses of oyster families with contrasted susceptibilities, we demonstrate that the disease is caused by multiple infection with an initial and necessary step of infection of oyster haemocytes by the Ostreid herpesvirus OsHV-1 µVar. Viral replication leads to the host entering an immune-compromised state, evolving towards subsequent bacteraemia by opportunistic bacteria. We propose the application of our integrative approach to decipher other multifactorial diseases that affect non-model species worldwide.

Highlights

Infectious diseases are mostly explored using reductionist approaches despite repeated evidence showing them to be strongly influenced by numerous interacting host and environmental factors
To characterize the complex dynamics determining the outcome of Pacific oyster mortality syndrome, we produced 15 biparental oyster families with highly contrasted resistance phenotypes with regard to the disease
The survival rates of Susceptible Family 11 (SF11) and Resistant Family 21 (RF21) oysters were measured concomitantly in a batch of oysters left on oyster farms; they showed identical phenotypes, with 2 and 98.1% survival after 384 h of exposure to the infectious environment for SF11 and RF21, respectively

Summary

Introduction

Infectious diseases are mostly explored using reductionist approaches despite repeated evidence showing them to be strongly influenced by numerous interacting host and environmental factors. There is a lack of understanding of some diseases triggering recurrent mass mortalities in non-model species of ecological and/or economic interest, such as pollinators, corals and marine molluscs[1,2,3] These dramatic epizooties remain incompletely characterized because epidemiological descriptions require holistic approaches to decipher the whole pathosystem. The objective of the present work was to examine one disease of complex aetiology affecting one of the most utilized invertebrate species in the world, the Pacific oyster Crassostrea gigas, applying a holistic approach to decipher the phenomenon This species has been introduced from Asia to numerous countries and is the main farmed oyster species worldwide[4]. The dynamics, relative weight and interactions of these different parameters in the disease remain to be established

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