Inhibitory Siglec-sialic acid interactions in balancing immunological activation and tolerance during viral infections

Saini, Pratima; Adeniji, Opeyemi S.; Abdel‐Mohsen, Mohamed

doi:10.1016/j.ebiom.2022.104354

Cited by 11 publications

(12 citation statements)

References 91 publications

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“…In viral infection, it is essential for a successful outcome that the immune response is powerful enough to eliminate the viral infection, yet controlled and specific enough to avoid unsustainable collateral damage to the host. In addition to being exploited by numerous microbes for attachment ( 2 ), sialic acids regulate host tolerance and immune activation by interacting with siglec-expressing immune cells ( 12 – 14 , 40 ). These interactions can be modulated by sialic acid O -acetylation ( 41 – 43 ).…”

Section: Discussionmentioning

confidence: 99%

“…First, how extensive is the RDE-mediated modulation of target cell surfaces in an infected individual? Second, considering that cell surface sialic acids modulate a range of cellular functions, including the activation of immune responses (12)(13)(14), could the loss of sialic acid viral receptors influence host biological functions with relevance to viral disease?…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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 anemia virus (ISAV) attaches to 4-O-acetylated sialic acids on Atlantic salmon epithelial, endothelial, and red blood cell surfaces. ISAV receptor binding and destruction are effectuated by the same 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 ISAV receptor 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. This links the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and shows that the observed effects are not mediated by endogenous esterases. Our findings are the first to directly link a viral RDE to extensive cell surface modulation in infected individuals. This raises the questions of whether other sialic acid-binding viruses that express RDEs affect host cells to a similar extent, and if such RDE-mediated cell surface modulation influences host biological functions with relevance to viral disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…The interplay between Siglecs and sialylated pathogens 74 -bacterial, viral and protozoan -represents an emergent field. It is expected to gain substantial momentum as we better understand how inhibitory Siglec-sialic acid interactions balance immunological activation and tolerance during viral infections, 75 the role of Siglecs in host defense and dissemination of enveloped viruses, 76 and infectious diseases more broadly, 75 including bacteria-induced sepsis 77 and infection associated with parasitic protozoa, such as Leishmania. 78 Sialic acids in Campylobacter jejuni lipooligosaccharide and auto-immune impacts Polysaccharides on bacterial surfaces are often implicated in molecular mimicry of host carbohydrate structures, 79 with sialic acids such as Neu5Ac, Neu5Gc, Pse and Leg playing a crucial albeit not fully understood role.…”

Section: Review Rsc Chemical Biologymentioning

confidence: 99%

Sialic acids in infection and their potential use in detection and protection against pathogens

Dedola,

Ahmadipour,

de Andrade

et al. 2024

RSC Chem. Biol.

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“…In viral infection, it is essential for a successful outcome that the immune response is powerful enough to eliminate the viral infection, but controlled and specific enough to avoid unsustainable collateral damage to the host. In addition to being exploited by numerous microbes for attachment [2], sialic acids regulate host tolerance and immune activation by interactions with siglec-expressing immune cells [12][13][14]39]. These interactions can be modulated by sialic acid O-acetylation [40][41][42].…”

Section: First Does the Rde-induced Cell Surface-modulation Influence...mentioning

confidence: 99%

“…First, how extensive is the RDE-mediated modulation of target cell surfaces in an infected individual? Second, considering that cell surface sialic acids modulate a range of cellular functions, including the activation of immune responses [12][13][14], could the loss of sialic acid viral receptors influence host biological functions with relevance to viral disease? Infectious salmon anaemia virus (Isavirus salaris, ISAV) is an enveloped, segmented, singlestranded, negative polarity RNA virus of the Orthomyxoviridae family.…”

Section: Introductionmentioning

confidence: 99%

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

Hol

Andresen

Ploss

et al. 2023

Preprint

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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.

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Inhibitory Siglec-sialic acid interactions in balancing immunological activation and tolerance during viral infections

Cited by 11 publications

References 91 publications

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

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

Sialic acids in infection and their potential use in detection and protection against pathogens

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

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