A nucleotide metabolic enzyme restricts viral lytic replication via protein deamidation.

Viral seasonality in the aquaculture industry is an important scientific issue for decades. While the molecular mechanisms underpinning the temperature-dependent pathogenesis of aquatic viral diseases remain largely unknown. Here we report that temperature-dependent activation of IL6-STAT3 signaling was exploited by grass carp reovirus (GCRV) to promote viral entry via increasing the expression of heat shock protein 90 (HSP90). Deploying GCRV infection as a model system, we discovered that GCRV induces the IL6-STAT3-HSP90 signaling activation to achieve temperature-dependent viral entry. Further biochemical and microscopic analyses revealed that the major capsid protein VP7 of GCRV interacted with HSP90 and relevant membrane-associated proteins to boost viral entry. Accordingly, exogenous expression of either IL6, HSP90, or VP7 in cells increased GCRV entry in a dose-dependent manner. Interestingly, other viruses (e.g., koi herpesvirus, Rhabdovirus carpio, Chinese giant salamander iridovirus) infecting ectothermic vertebrates have evolved a similar mechanism to promote their infection. This work delineates a molecular mechanism by which an aquatic viral pathogen exploits the host temperature-related immune response to promote its entry and replication, instructing us on new ways to develop targeted preventives and therapeutics for aquaculture viral diseases.

The seasonality of viral diseases in ectotherms is a prevailing phenomenon in the aquatic environment, which causes huge economic losses every year worldwide and hinders sustainable development of the aquaculture industry. Nevertheless, our understanding of the molecular mechanism of how temperature determines the pathogenesis of aquatic viruses remains largely unexplored.

Cadmium (Cd) is one of the dominant metal pollutants present in the aquatic environment that affects ion homeostasis, oxidative stress (OS) and immune responses of aquatic organisms. Given the physicochemical similarities between Cd²⁺ and calcium (Ca²⁺) ions, their antagonism may facilitate the mitigation of Cd-induced toxicity. To better understand the role of Ca in protecting against Cd-induced toxicity in teleosts, juvenile grass carp were exposed to Cd (measured concentration 3 μg/L) and a gradient of Ca concentrations (measured concentration 1.5 mg/L, 2.5 mg/L, 3.0 mg/L, and 3.5 mg/L in the control (CTL) group, low calcium (LCA) group, medium calcium (MCA) group, and high calcium (HCA) group, respectively) for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) data analyses showed that simultaneous exposure to Ca impaired the accumulation of Cd in all tested tissues. Besides, Ca addition maintained the plasma ion (Na⁺, K⁺, Cl^-) homeostasis, alleviated Cd-induced oxidative stress (OS), and regulated the activities and transcriptional levels of ATPase. Furthermore, transcriptional heatmap analysis demonstrated that several indicator genes for OS and calcium signaling pathway were found to be significantly modulated by Ca addition. This work delineates a protective effect of Ca against Cd-induced toxicity in grass carp, providing new insight into the possible solutions to Cd pollution issues in aquaculture industry.

The ancestors of chemokines originate in the most primitive of vertebrates, which has recently attracted great interest in the immune functions and the underlying mechanisms of fish chemokines. In the current study, we identified an evolutionarily conserved chemokine, CiCXCL13, from a teleost fish, grass carp. CiCXCL13 was characterized by a typical SCY (small cytokine CXC) domain and four cysteine residues (C34, C36, C61, C77), with the first two cysteines separated by a random amino acid residue, although it shared 24.2–54.8% identity with the counterparts from other vertebrates. CiCXCL13 was an inducible chemokine, whose expression was significantly upregulated in the immune tissues of grass carps after grass carp reovirus infection. CiCXCL13 could bind to the membrane of grass carp head kidney leukocytes and promote cell migration, NO release, and the expression of >15 inflammatory cytokines, including IL-1β, TNF-α, IL-10 and TGF-β1, thus regulating the inflammatory response. Mechanistically, CiCXCL13 interacted with its evolutionarily conserved receptor CiCXCR5 and activated the Akt–NF-κB and p38–AP-1 pathways, as well as a previously unrevealed p38–NF-κB pathway, to efficiently induce inflammatory cytokine expression, which was distinct from that reported in mammals. Zebrafish CXCL13 induced inflammatory cytokine expression through Akt, p38, NF-κB, and AP-1 as CiCXCL13. Meanwhile, the CiCXCL13–CiCXCR5 axis–mediated inflammatory activity was negatively shaped by grass carp atypical chemokine receptor 2 (CiACKR2). The present study is, to our knowledge, the first to comprehensively define the immune function of CXCL13 in inflammatory regulation and the underlying mechanism in teleosts, and it provides a valuable perspective on the evolution and biology of fish chemokines.