Biology subjects

Andresen, A. M. S.

Publications and source records attributed to Andresen, A. M. S..

3 recordsLinked to original sources

bioRxiv2026

Common ISAV haemagglutinin esterase variants at residues 229 and 230 influence the efficiency of receptor destruction and erythrocyte release in Atlantic salmon

Sialic acid-binding viruses often encode receptor-destroying enzymes that modulate infection through host glycan alteration. Isavirus salaris (ISAV), the aetiological agent of infectious salmon anaemia, encodes a haemagglutinin esterase with 4-O-acetylesterase activity. The ISAV esterase removes the virus-targeted epitope and causes homologous attachment interference, but its broader biological roles remain poorly understood. Several aspects of ISAV receptor engagement and release remain unresolved: Although ISAV agglutinates erythrocytes from both rainbow trout and Atlantic salmon, only rainbow trout erythrocytes elute from this interaction. By contrast, Atlantic salmon erythrocytes remain persistently bound, despite the presence of an active esterase. Here, we used ISAV-erythrocyte interactions to dissect receptor destruction and dissociation across viral genotypes and strains. We uncovered substantial functional diversity in viral permissiveness for Atlantic salmon erythrocyte elution. Common variants of residues 229 and 230 of the haemagglutinin-esterase, located at the distal rim of the P1 esterase pocket, were key determinants of elution permissiveness. Elution further required an active esterase catalytic triad. In vivo, Atlantic salmon infected with ISAV carrying the elution-permissive 229N variant showed earlier loss of erythrocyte Neu4,5Ac2 than fish infected with an elution-restrictive strain. The loss of Neu4,5Ac2 preceded the reduction in ISAV-bound erythrocytes by several days, indicating that receptor removal alone was insufficient to trigger virion release. Targeted sialic acid analyses revealed similar levels of Neu4,5Ac2 on Atlantic salmon and rainbow trout erythrocytes. Atlantic salmon erythrocytes additionally expressed di-O-acetylated Neu4,5,9Ac3. By contrast, brown trout erythrocytes expressed little or no Neu4,5Ac2, consistent with their reported inability to support ISAV haemagglutination. Together, our findings give insight into viral and host determinants of ISAV receptor interactions. We demonstrate functional diversity within the ISAV esterase and link virion binding and release to salmonid erythrocyte sialic acid composition. The delay between receptor loss and virion dissociation further supports the existence of additional erythrocyte attachment factors.

microbiology↗

bioRxiv2025

Virus-inclusive single-nucleus RNA sequencing reveals two distinct endothelial response patterns in infectious salmon anaemia.

Viral replication in endothelial cells is a hallmark of many viral diseases in humans and other animals, underscoring the importance of understanding cellular mechanisms that restrict viral replication and the associated consequences for vascular health. Pathogenic variants of infectious salmon anaemia virus (ISAV, Isavirus salaris) target endothelial cells of Atlantic salmon (Salmo salar L.), causing severe systemic disease and major losses during outbreaks in aquaculture. To better understand the endothelial response to ISAV, we used single nucleus RNA-sequencing at pre-clinical (12 days post infection, dpi) and clinical (16 dpi) stages of infection. Our approach enables an assessment of transcriptomic responses for different endothelial subpopulations at unprecedented resolution. ISAV RNA was predominantly detected in endothelial cells, which, along with mononuclear phagocytes, showed the highest number of differentially regulated genes at both time points. At 12 dpi, differentially expressed genes in endothelial cells were enriched for pathways related to NOD-like receptor signaling, antiviral responses, and regulation of programmed cell death. By 16 dpi, we observed a shift toward enrichment of pathways associated with cellular senescence, apelin signaling, and insulin signaling. We identified two distinct infection-related states at both time points: a virus-permissive state characterized by upregulation of genes involved in protein synthesis, small GTPase signaling, and MAPK activity, and a bystander phenotype marked by activation of antiviral responses, immune signaling, and translational regulation. This study is the first to capture the individual cell type responses to ISAV infection, and to characterize the in vivo endothelial response to active viral replication at single-cell resolution in any species.

immunology↗

bioRxiv2023

The infectious salmon anaemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition

Many sialic acid-binding viruses express a receptor-destroying enzyme (RDE) that removes the virus-targeted receptor and limits viral interactions with the host cell surface. Despite a growing appreciation of how the viral RDE promotes viral fitness, little is known about its direct effects on the host. Infectious salmon anaemia virus (ISAV) attaches to 4-O-acetylated sialic acids on the surface of Atlantic salmon epithelial, endothelial, and red blood cells. ISAV receptor binding and destruction are effectuated by the same surface molecule, the haemagglutinin esterase (HE). We recently discovered a global loss of vascular 4-O-acetylated sialic acids in ISAV-infected fish. The loss correlated with the expression of viral proteins, giving rise to the hypothesis that it was mediated by the HE. Here, we report that the capacity to bind new ISAV particles is also progressively lost from circulating erythrocytes in infected fish. Furthermore, salmon erythrocytes exposed to ISAV ex vivo lost their capacity to bind new ISAV particles. The loss of ISAV binding was not associated with receptor saturation. Moreover, upon loss of the ISAV receptor, erythrocyte surfaces became more available to the lectin wheat germ agglutinin, suggesting a potential to alter interactions with endogenous lectins of similar specificity. The pruning of erythrocyte surfaces was inhibited by an antibody that prevented ISAV attachment. Furthermore, recombinant HE, but not an esterase-silenced mutant, was sufficient to induce the observed surface modulation. Our results directly link the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and show that the observed effects are not mediated by endogenous esterases. Our findings are the first to directly link a viral esterase to extensive host cell surface modulation in infected individuals. This raises the question of how common the phenomenon is among sialic acid-binding viruses. It is also relevant to ask if the altered sialic acid landscape of the affected cells influences host biological functions with relevance to viral disease.

microbiology↗