scholarly journals Mucosal and Systemic Immune Responses to Salmon Gill Poxvirus Infection in Atlantic Salmon Are Modulated Upon Hydrocortisone Injection

2021 ◽  
Vol 12 ◽  
Author(s):  
Marit M. Amundsen ◽  
Haitham Tartor ◽  
Kathrine Andersen ◽  
Karoline Sveinsson ◽  
Even Thoen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Atlantic Salmon ◽  
Apoptotic Cell ◽  
Cell Activity ◽  
Mucosal Immune Response ◽  
Antiviral Immune Response ◽  
Clinical Phase ◽  
Hormone Injection ◽  
Gill Pathology

Salmon Gill Poxvirus Disease (SGPVD) has emerged as a cause of acute mortality in Atlantic salmon (Salmo salar L.) presmolts in Norwegian aquaculture. The clinical phase of the disease is associated with apoptotic cell death in the gill epithelium causing acute respiratory distress, followed by proliferative changes in the regenerating gill in the period after the disease outbreak. In an experimental SGPV challenge trial published in 2020, acute disease was only seen in fish injected with hydrocortisone 24 h prior to infection. SGPV-mediated mortality in the hydrocortisone-injected group was associated with more extensive gill pathology and higher SGPV levels compared to the group infected with SGPV only. In this study based on the same trial, SGPV gene expression and the innate and adaptive antiviral immune response was monitored in gills and spleen in the presence and absence of hydrocortisone. Whereas most SGPV genes were induced from day 3 along with the interferon-regulated innate immune response in gills, the putative SGPV virulence genes of the B22R family were expressed already one day after SGPV exposure, indicating a potential role as early markers of SGPV infection. In gills of the hydrocortisone-injected fish infected with SGPV, MX expression was delayed until day 10, and then expression skyrocketed along with the viral peak, gill pathology and mortality occurring from day 14. A similar expression pattern was observed for Interferon gamma (IFNγ) and granzyme A (GzmA) in the gills, indicating a role of acute cytotoxic cell activity in SGPVD. Duplex in situ hybridization demonstrated effects of hydrocortisone on the number and localization of GzmA-containing cells, and colocalization with SGPV infected cells in the gill. SGPV was generally not detected in spleen, and gill infection did not induce any corresponding systemic immune activity in the absence of stress hormone injection. However, in fish injected with hydrocortisone, IFNγ and GzmA gene expression was induced in spleen in the days prior to acute mortality. These data indicate that suppressed mucosal immune response in the gills and the late triggered systemic immune response in the spleen following hormonal stress induction may be the key to the onset of clinical SGPVD.

scholarly journals IFN-I Independent Antiviral Immune Response to Vesicular Stomatitis Virus Challenge in Mouse Brain

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 326
Author(s):  
Anurag R. Mishra ◽  
Siddappa N. Byrareddy ◽  
Debasis Nayak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vesicular Stomatitis Virus ◽  
Antiviral Response ◽  
Type I ◽  
Immune Gene ◽  
Antiviral Immune Response ◽  
Virus Challenge ◽  
Vesicular Stomatitis ◽  
Ifn Γ

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role of IFN-I in the CNS against viral encephalitis is not entirely clear. Here we have implemented the combination of global differential gene expression profiling followed by bioinformatics analysis to decipher the CNS immune response in the presence and absence of the IFN-I signaling. We observed that vesicular stomatitis virus (VSV) infection induced 281 gene changes in wild-type (WT) mice primarily associated with IFN-I signaling. This was accompanied by an increase in antiviral response through leukocyte vascular patrolling and leukocyte influx along with the expression of potent antiviral factors. Surprisingly, in the absence of the IFN-I signaling (IFNAR−/− mice), a significantly higher (1357) number of genes showed differential expression compared to the WT mice. Critical candidates such as IFN-γ, CCL5, CXCL10, and IRF1, which are responsible for the recruitment of the patrolling leukocytes, are also upregulated in the absence of IFN-I signaling. The computational network analysis suggests the presence of the IFN-I independent pathway that compensates for the lack of IFN-I signaling in the brain. The analysis shows that TNF-α is connected maximally to the networked candidates, thus emerging as a key regulator of gene expression and recruitment of myeloid cells to mount antiviral action. This pathway could potentiate IFN-γ release; thereby, synergistically activating IRF1-dependent ISG expression and antiviral response.

scholarly journals Gene expression response to sea lice in Atlantic salmon skin: an RNA-Seq comparison between resistant and susceptible animals

2017 ◽  
Author(s):  
Diego Robledo ◽  
Alejandro P. Gutiérrez ◽  
Agustín Barría ◽  
José M. Yáñez ◽  
Ross D. Houston
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Atlantic Salmon ◽  
Host Resistance ◽  
Sea Lice ◽  
Economic Losses ◽  
Rna Seq ◽  
Healthy Skin ◽  
Novel Treatment ◽  
Attachment Sites

ABSTRACTBackgroundSea lice are parasitic copepods that cause large economic losses to salmon aquaculture worldwide. Frequent chemotherapeutic treatments are typically required to control this parasite, and alternative measures such as breeding for improved host resistance are desirable. Insight into the host-parasite interaction and mechanisms of host resistance can lead to improvements in selective breeding, and potentially novel treatment targets. In this study, RNA sequencing was used to study the skin transcriptome of Atlantic salmon parasitized with sea lice (C. rogercresseyi). The overall aims were to compare the transcriptomic profile of skin at louse attachment sites and ‘healthy’ skin, and to assess differences between animals with varying levels of resistance to the parasite.ResultsAtlantic salmon were challenged with C. rogercresseyi, growth and lice count measurements were taken for each fish. 21 animals were selected and RNA-Seq was performed on skin from a louse attachment site, and skin distal to attachment sites for each animal. These animals were classified into family-balanced groups according to the traits of resistance (high vs low lice count), and growth during infestation (an indication of tolerance). Overall comparison of skin from louse attachment sites versus healthy skin showed that 4,355 genes were differentially expressed, indicating local up-regulation of several immune pathways and activation of tissue repair mechanisms. Comparison between resistant and susceptible animals highlighted expression differences in several immune response and pattern recognition genes, and also myogenic and iron availability factors. Genomic regions showing signs of differentiation between resistant and susceptible fish were identified using an Fst analysis.ConclusionsComparison of the skin transcriptome between louse attachment sites and healthy skin has yielded a detailed profile of genes and pathways with putative roles in the local host immune response to C. rogercresseyi. The difference in skin gene expression profile between resistant and susceptible animals led to the identification of several immune and myogenic pathways potentially involved in host resistance. Components of these pathways may be targets for studies aimed at improved or novel treatment strategies, or to prioritise candidate functional polymorphisms to enhance genomic selection for host resistance in commercial salmon farming.

scholarly journals Deletion of the K1L Gene Results in a Vaccinia Virus That Is Less Pathogenic Due to Muted Innate Immune Responses, yet Still Elicits Protective Immunity

2017 ◽  
Vol 91 (15) ◽  
Author(s):  
Ariana G. Bravo Cruz ◽  
Aiguo Han ◽  
Edward J. Roy ◽  
Arielle B. Guzmán ◽  
Rita J. Miller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Virus Replication ◽  
Protective Immunity ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Antiviral Immune Response

ABSTRACT All viruses strategically alter the antiviral immune response to their benefit. The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in tissue culture models of infection, including NF-κB antagonism. However, the effect of K1 during animal infection is poorly understood. We determined that a K1L-less vaccinia virus (vΔK1L) was less pathogenic than wild-type VACV in intranasal and intradermal models of infection. Decreased pathogenicity was correlated with diminished virus replication in intranasally infected mice. However, in intradermally inoculated ears, vΔK1L replicated to levels nearly identical to those of VACV, implying that the decreased immune response to vΔK1L infection, not virus replication, dictated lesion size. Several lines of evidence support this theory. First, vΔK1L induced slightly less edema than vK1L, as revealed by histopathology and noninvasive quantitative ultrasound technology (QUS). Second, infiltrating immune cell populations were decreased in vΔK1L-infected ears. Third, cytokine and chemokine gene expression was decreased in vΔK1L-infected ears. While these results identified the biological basis for smaller lesions, they remained puzzling; because K1 antagonizes NF-κB in vitro, antiviral gene expression was expected to be higher during vΔK1L infection. Despite these diminished innate immune responses, vΔK1L vaccination induced a protective VACV-specific CD8+ T cell response and protected against a lethal VACV challenge. Thus, vΔK1L is the first vaccinia virus construct reported that caused a muted innate immune gene expression profile and decreased immune cell infiltration in an intradermal model of infection yet still elicited protective immunity. IMPORTANCE The vaccinia virus (VACV) K1 protein inhibits NF-κB activation among its other antagonistic functions. A virus lacking K1 (vΔK1L) was predicted to be less pathogenic because it would trigger a more robust antiviral immune response than VACV. Indeed, vΔK1L was less pathogenic in intradermally infected mouse ear pinnae. However, vΔK1L infection unexpectedly elicited dramatically reduced infiltration of innate immune cells into ears. This was likely due to decreased expression of cytokine and chemokine genes in vΔK1L-infected ears. As such, our finding contradicted observations from cell culture systems. Interestingly, vΔK1L conferred protective immunity against lethal VACV challenge. This suggests that the muted immune response triggered during vΔK1L infection remained sufficient to mount an effective protective response. Our results highlight the complexity and unpredictable nature of virus-host interactions, a relationship that must be understood to better comprehend virus pathogenesis or to manipulate viruses for use as vaccines.

scholarly journals Inhibition of NF-κB Activation in Combination with Bcl-2 Expression Allows for Persistence of First-Generation Adenovirus Vectors in the Mouse Liver

1998 ◽  
Vol 72 (11) ◽  
pp. 9267-9277 ◽  
Author(s):  
André Lieber ◽  
Chen-Yi He ◽  
Leonard Meuse ◽  
Charis Himeda ◽  
Christopher Wilson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Transgenic Mice ◽  
Transcriptional Activation ◽  
First Generation ◽  
Viral Gene ◽  
Gene Products ◽  
Antiviral Immune Response ◽  
Innate Defense ◽  
Adenovirus Vectors

ABSTRACT NF-κB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and activation of inflammatory cells. We reported earlier that viral gene expression in hepatocytes transduced with first-generation (E1-deleted) adenoviruses induced NF-κB activation, elevation of serum cytokines, and hepatocellular apoptosis during the first days postinfusion. These events did not occur in mice infused with an adenovirus vector deleted for E1, E2, E3, and late gene expression. In the present study, we used an adenovirus expressing an IκBα supersuppressor (Ad.IκBM) andbcl-2 transgenic mice to unravel the role of virus-induced NF-κB activation and apoptosis in the clearance of recombinant adenovirus vectors from the liver. The combined action of IκBM and Bcl-2 allowed for vector persistence in livers of C57BL/6 × C3H mice. In the absence of Bcl-2, IκBM expression in mouse livers significantly reduced NF-κB activation, cytokine expression, leukocyte infiltration, and the humoral immune response against the transgene product; however, this was not sufficient to prevent the decline of vector DNA in transduced cells. Infusion of Ad.IκBM caused extended apoptosis predominantly in periportal liver regions, indicating that NF-κB activation may protect transduced hepatocytes from apoptosis induced by adenovirus gene products. To confer vector persistence, bcl-2 transgene expression was required to block virus-induced apoptosis if NF-κB protection was inactivated by IκBM. Expression of gene products involved in early stages of apoptotic pathways was up-regulated in response to virus infusion inbcl-2 transgenic mice, which may represent a compensatory effect. Our study supports the idea that the suppression of innate defense mechanisms improves vector persistence.

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