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.

International audienceSince 2008, mass mortalities of 1-yr-old Crassostrea gigas associated with the ostreid herpesvirus OsHV-1 μVar have occurred along all the coasts of France when seawater temperature reaches 16 to 17°C. The present study aimed to characterize the effect of temperature on oyster survival in combination with OsHV-1 DNA quantification by standard real-time PCR and total vibrio population levels in oyster tissues. To examine the effect of seawater temperature on disease transmission and related mortality of oysters, cohabitation experiments were conducted between healthy naïve oysters and oysters previously exposed to field conditions in areas where mortalities were occurring. Oysters initially maintained in controlled conditions (free of mortality and negative for OsHV-1), and then transferred to an area where high mortalities were occurring among farmed stocks, became infected with OsHV-1 and exhibited high loads of vibrios followed by significant mortalities. When previously exposed oysters were maintained indoors at 13.0°C for 40 d and then at 20.6°C, they exhibited no mortality, were negative for OsHV-1 detection, and did not transmit the disease to healthy oysters. Survival of previously exposed oysters maintained indoors at 8 temperatures ranging from 13.4 to 29.0°C varied from 25 to 48% and was negatively correlated with holding temperature. Concomitantly, survival of naïve cohabiting animals (62 to 98%) decreased with increasing seawater temperature until a plateau was reached between 16.2 and 21.9°C, and increased at higher temperatures. Therefore, the optimal temperature range for disease transmission from field-exposed to naïve animals was between 16.2 and 21.9°C. Our results suggest that a long-term period (40 d) at low temperature (13°C) may offer a method of mitigating mortalities in oysters that have been exposed to an infective environment

Mortalities of oyster Crassostrea gigas seed associated with ostreid herpesvirus OsHV-1 μVar have been observed in many oyster-producing countries since 2008. The present study, comprised of 4 complementary experiments, aimed to identify factors associated with disease-induced oyster mortality in order to propose mitigation strategies. Our first experiment compared survival of oysters from natural spatfall with others sampled from nurseries, after thermal elevation in the laboratory from <14 to 21°C. A total of 60% of the tested wild seed batches (n = 51) were infected by OsHV-1, exhibited mortality and were able to transmit the disease to cohabited naïve oysters. Comparatively, only 1 out of the 32 tested batches sampled from nurseries presented similar characteristics. In a second experiment, we studied the effects that timing and duration of exposure to field conditions had on risk of infection and mortality in the laboratory at 21°C. Naïve oysters deployed in the field during winter and spring, when seawater temperatures were <14.7°C, showed no mortality in the laboratory, and OsHV-1 DNA was not detected by PCR. However, in oysters transferred to the field, OsHV-1 was observed when seawater temperature reached ~15.3°C. Our third experiment showed that the odds of mortality decreased with age of oysters when facing the disease. Further, we observed that odds of disease mortality decreased with water renewal and increased with the biomass of neighbouring infected oysters under controlled conditions. Based on these findings, we propose mitigation strategies in terms of the regulation of oyster movements between sites, timing of seeding and spatial planning, taking into account seawater temperature and seed origin