Biology subjects

Gratacap, R.

Publications and source records attributed to Gratacap, R..

3 recordsLinked to original sources

bioRxiv2022

Transcriptomic response to ISAV infection in the gills, head kidney and spleen of resistant and susceptible Atlantic salmon

BackgroundInfectious Salmonid Anaemia virus (ISAV) is an orthomyxovirus responsible of large losses in Atlantic salmon (Salmo salar) aquaculture. Current available treatments and vaccines are not fully effective, and therefore selective breeding to produce ISAV-resistant strains of Atlantic salmon (Salmo salar) is a high priority for the industry. Genomic selection and potentially genome editing can be applied to enhance the disease resistance of aquaculture stocks, and both approaches can benefit from increased knowledge on the genomic mechanisms of resistance to ISAV. To improve our understanding of the mechanisms underlying resistance to ISAV in Atlantic salmon we performed a transcriptomic study in ISAV-infected salmon with contrasting levels of resistance to this virus. ResultsThree different tissues (gills, head kidney and spleen) were collected on 12 resistant and 12 susceptible fish at three timepoints (pre-challenge, 7 and 14 days post infection) and RNA sequenced. The transcriptomes of Infected and non-infected fish and of resistant and susceptible fish were compared at each timepoint. The results show that the responses to ISAV are organ-specific; an important response to the infection was observed in the head kidney, with up-regulation of immune processes such as interferon and NLR pathways, while in gills and spleen the response was more moderate. In addition to immune related genes our results suggest that other processes such as ubiquitination or ribosomal processing are important during early infection to ISAV. Moreover, the comparison between resistant and susceptible have also highlighted some interesting genes related to ubiquitination, intracellular transport or the inflammasome. ConclusionsAtlantic salmon infection by ISAV revealed an organ-specific response, implying differential function during the infection. An early immune response was observed in the head kidney, while gills and spleen showed modest responses in comparison. Comparison between resistance and susceptible samples have highlighted genes of interest for further studies, for instance those related to ubiquitination or the inflammasome.

genomics↗

bioRxiv2022

Understanding host response to infectious salmon anaemia virus in an Atlantic salmon cell line using single-cell RNA sequencing

BackgroundInfectious Salmon Anaemia Virus (ISAV) is an Orthomixovirus that currently represents a large problem for salmonid aquaculture worldwide. Prevention and treatment methods are only partially effective. Genetic selection and genome engineering strategies have potential to develop ISAV resistant salmon stocks. However, this requires a detailed understanding of the genomic regulation of ISAV pathogenesis. Here, we used single cell RNA sequencing on a salmonid cell line to provide a high dimensional insight into the transcriptional landscape that underpin host-virus interactions during ISAV infection at the single cell level. ResultsSalmon head kidney 1 (SHK-1) cells were single-cell RNA sequenced before challenge, and at 24h, 48h, and 96h post-ISAV challenge. The results revealed marked changes in the host transcriptome at 48h and 96h post-infection, even in uninfected cells, potentially suggesting paracrine signalling. This paracrine activation of uninfected cells seemed to be unspecific, involving pathways such as mRNA sensing, ubiquitination or proteasome, and also the up-regulation of the mitochondrial ribosome genes. At 24h post infection, cells showed expression signatures consistent with viral entry, with up-regulation of genes such as PI3K, FAK or JNK. At 48h and 96h, infected cells showed a clear anti-viral response, characterised by the expression of IFNA2 or IRF2. ConclusionsThis study has increased our understanding of the cellular response of Atlantic salmon during ISAV infection, and revealed potential host-virus interactions at the cellular level. The results highlight the value of single-cell sequencing to characterise cell culture models of viral infection, and the results can be exploited in future functional studies to increase the resistance of Atlantic salmon to ISAV.

genomics↗

bioRxiv2020

Exploring genetic resistance to Infectious Salmon Anaemia Virus in Atlantic salmon by genome-wide association and RNA sequencing

Infectious Salmonid Anaemia Virus (ISAV) causes a notifiable disease that poses a large threat for Atlantic salmon breeders and producers worldwide. There is no fully effective treatment or vaccine, and therefore selective breeding to increase resistance to ISAV in commercial strains of Atlantic salmon is a promising avenue for disease prevention. Genomic selection and potentially genome editing can be applied to enhance host resistance, and these approaches benefit from improved knowledge of the genetic and functional basis of the target trait. The aim of this study was to characterise the genetic architecture of resistance to ISAV in a commercial Atlantic salmon population and study its underlying functional genomic basis using RNA Sequencing. A total of 2,833 Atlantic salmon parr belonging to 194 families were exposed to ISAV in a cohabitation challenge in which cumulative mortality reached 63% over 55 days. A total of 1,353 animals were genotyped using a 55K SNP array, and the estimate of heritability for the trait of binary survival was 0.33 ({+/-}0.04). A genome-wide association analysis confirmed that resistance to ISAV was a polygenic trait, albeit a genomic region in chromosome 13 was significantly associated with resistance and explained 3% of the genetic variance. RNA sequencing of the heart of 16 infected (7 and 14 days post infection) and 8 control fish highlighted 4,927 and 2,437 differentially expressed genes at 7 and 14 days post infection respectively. The complement and coagulation pathway was down-regulated, while several metabolic pathways were up-regulated in infected fish compared to controls. The interferon pathway was mildly activated at 7 days and showed no sign of up-regulation at 14 days post infection, implying a crosstalk between host and virus. Comparison of the transcriptomic response of fish with high and low breeding values for resistance (4 high resistance and 4 low resistance animals per time point) highlighted TRIM25 as being up-regulated in resistant fish, suggesting it may be a key antiviral gene involved in the functional genetic basis of resistance to ISAV.

genetics↗