Glycan structures and antiviral effect of the structural subunit RvH2 of Rapana hemocyanin

Dolashka, Pavlina; Velkova, Lyudmila; Shishkov, Stoyan; Kostova, Kalina; Dolashki, Aleksander; Димитров, Иван; Атанасов, Б.; Devreese, Bart; Voelter, Wolfgang; Beeumen, Jozef Van

doi:10.1016/j.carres.2010.08.005

Cited by 40 publications

(47 citation statements)

References 38 publications

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“…Thus, the present data support this assumption and suggest potential mechanisms, but they do not provide evidence on the cause of these differences. We think that differences in the intrinsic structural features of these proteins are the key to activation of APCs, and several authors have proposed that sugar moieties may play a role during the immune response against hemocyanins (4,8,26,29). Because mannose is the major sugar found in these proteins, we proposed that APCs might recognize mollusk hemocyanins as a "highly mannosylated infectious agent" (6).…”

Section: Discussionmentioning

confidence: 93%

“…FLH is composed of a single type of subunit that forms homodidecamers (8). Another significant feature of the hemocyanin structure is the presence of carbohydrates, as heterogeneous N-and O-glycosylation ramifications, with mannose being the common and most abundant oligosaccharide (25)(26)(27)(28)(29)(30). Although the three hemocyanins present N-and O-linked oligosaccharides, there are differences in their arrangements.…”

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confidence: 99%

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Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages

Zhong

Arancibia

Born

et al. 2016

The Journal of Immunology

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Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5. Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages

Zhong

Arancibia

Born

et al. 2016

The Journal of Immunology

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“…Molluscan hemocyanins, copper-containing oxygen transport macromolecules, have also been observed to be multifunctional, with innate immune functions, including antiviral activity, as demonstrated against the herpesviruses herpes simplex virus (HSV) and Epstein-Barr virus (EBV), in the abalone H. rubra (51) and the veined whelk Rapana venosa (32,43). These observations were extended to include Rapana venosa activity against HSV-1 and HSV-2 (39).…”

Section: Structures and Mechanisms Of Action Of Molluscan Antiviral Cmentioning

confidence: 92%

“…To date, most characterized extracts from mollusc species with in vitro antiviral activity have been peptides or glycopeptides, for example, kelletinin A from Buccinulum corneum (40), glycosylated functional unit RtH2 of hemocyanin from Rapana venosa (27,32,39), mytilin and defensin from Mytilus galloprovincialis (29,38), and lectin from Crenomytilus grayanus (37). Their modes of action are not fully characterized; however, they appear to include direct inactivation of virus and prevention of viral attachment to or entry into host cells or inhibition of viral transcription and DNA or RNA synthesis (Table 1).…”

Section: Structures and Mechanisms Of Action Of Molluscan Antiviral Cmentioning

confidence: 99%

Marine Snails and Slugs: a Great Place To Look for Antiviral Drugs

Vinh

Benkendorff

Green

et al. 2015

J Virol

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e Molluscs, comprising one of the most successful phyla, lack clear evidence of adaptive immunity and yet thrive in the oceans, which are rich in viruses. There are thought to be nearly 120,000 species of Mollusca, most living in marine habitats. Despite the extraordinary abundance of viruses in oceans, molluscs often have very long life spans (10 to 100 years). Thus, their innate immunity must be highly effective at countering viral infections. Antiviral compounds are a crucial component of molluscan defenses against viruses and have diverse mechanisms of action against a wide variety of viruses, including many that are human pathogens. Antiviral compounds found in abalone, oyster, mussels, and other cultured molluscs are available in large supply, providing good opportunities for future research and development. However, most members of the phylum Mollusca have not been examined for the presence of antiviral compounds. The enormous diversity and adaptations of molluscs imply a potential source of novel antiviral compounds for future drug discovery.

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“…The high carbohydrate content of hemocyanins, up to 9% (w/w), has been measured by different methods, including the use of lectins and high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The presence of numerous N-glycosylation sites and a reduced number of Owww.intechopen.com glycosylation sites has been established (Dolashka-Angelova et al, 2003;Gielens et al, 2004;Idakieva et al, 2004;Gatsogiannis & Markl, 2009;Dolashka et al, 2010). Mollusk hemocyanins contain diverse sugar moieties, including mannose, D-galactose, fucose, N-acetyl-Dgalactosamine and N-acetyl-glucosamine residues, with mannose being the most abundant (Harris & Markl, 1999).…”

Section: Structure Of the Mollusk Hemocyaninsmentioning

confidence: 99%