Increased Antiviral and Opsonic Activity of a Highly Multimerized Collectin Chimera

White, Mitchell R.; Crouch, Erika C.; Chang, Donald; Hartshorn, Kevan L.

doi:10.1006/bbrc.2001.5373

Cited by 29 publications

(27 citation statements)

References 22 publications

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“…C-type lectin SP-D plays a key role in the defense against influenza virus infection through the recognition of mannose residue on the viral hemagglutinin with CRDs and thereby inhibits early stages of viral infection (52). SP-D also binds to neuraminidase and inhibits its activity (51).…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Yang

Chen

Wang

et al. 2011

J Virol

107

124

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Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactosecontaining oligosaccharides. Since the envelope proteins of influenza virus are highly glycosylated, we studied the role of galectin-1 in influenza virus infection in vitro and in mice. We found that galectin-1 was upregulated in the lungs of mice during influenza virus infection. There was a positive correlation between galectin-1 levels and viral loads during the acute phase of viral infection. Cells treated with recombinant human galectin-1 generated lower viral yields after influenza virus infection. Galectin-1 could directly bind to the envelope glycoproteins of influenza A/WSN/33 virus and inhibit its hemagglutination activity and infectivity. It also bound to different subtypes of influenza A virus with micromolar dissociation constant (K d ) values and protected cells against influenza virus-induced cell death. We used nanoparticle, surface plasmon resonance analysis and transmission electron microscopy to further demonstrate the direct binding of galectin-1 to influenza virus. More importantly, we show for the first time that intranasal treatment of galectin-1 could enhance survival of mice against lethal challenge with influenza virus by reducing viral load, inflammation, and apoptosis in the lung. Furthermore, galectin-1 knockout mice were more susceptible to influenza virus infection than wild-type mice. Collectively, our results indicate that galectin-1 has anti-influenza virus activity by binding to viral surface and inhibiting its infectivity. Thus, galectin-1 may be further explored as a novel therapeutic agent for influenza.

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Section: Discussionmentioning

confidence: 99%

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Yang

Chen

Wang

et al. 2011

J Virol

107

124

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“…Increasing the extent of multimerization of SP-D increases the antiviral activity of this molecule (13,15). It has been proposed that differences in multimerization could be age or disease related or could result from polymorphisms of SP-D genes that influence assembly (15).…”

Section: Discussionmentioning

confidence: 99%

Surfactant Protein D Gene Polymorphism Associated with Severe Respiratory Syncytial Virus Infection

et al. 2002

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Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (Ϯ2 wk) and gestational age at birth (Ϯ2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p ϭ 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p ϭ 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection. Respiratory syncytial virus (RSV) is a major respiratory tract pathogen in early childhood. In young infants, seasonal epidemics of RSV cause 50% of the severe instances of bronchiolitis that require hospital treatment and may be fatal. Environmental factors, gender, and socioeconomic status all play a role in RSV infections, but the host-related differences in susceptibility suggest that genetic factors contribute to the risk of contracting this disease (1).Pulmonary surfactant, a complex mixture of phospholipids and surfactant proteins, lines the alveolar surface of the lung and is essential for normal respiratory function. Surfactant protein D (SP-D) was first described in association with alveolar surfactant. However, this protein does not bind to the surfactant complex and has been found elsewhere in the airways. SP-D is a collagenous C-type lectin mainly assembled as dodecamers consisting of four homotrimeric subunits. SP-D has several immunomodulatory functions, including agglutination of some viruses that cause airway disease (2).Concentrations of the surfactant components are decreased in viral bronchiolitis (3, 4). Studies with a mouse model have shown dysfunction of the surfactant complex in RSV induced pulmonary infections (5). Hickling et al. (6) showed that intranasal administration of recombinant SP-D domain to RSV-infected mice reduced the levels of lung virus by 80%, suggesting that SP-D plays a major role in clearing RSV from the lu...

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“…Both proteins are N-glycosylated in their CRDs and the protocols used to enzymatically remove the N-linked carbohydrates from pSP-D and pSP-A proved efficient. Because many interactions of SP-D with IAV are affected by the degree of multimerization of SP-D (25,39,40), the size of pSP-D before and after N-glycanase treatment was analyzed by gel filtration chromatography and revealed no detectable differences between both preparations (Ͼ1500 kDa). Therefore, it can be concluded that N-glycanase treatment of pSP-D did not seriously alter its multimer size.…”

Section: Discussionmentioning

confidence: 99%

Porcine Pulmonary Collectins Show Distinct Interactions with Influenza A Viruses: Role of theN-Linked Oligosaccharides in the Carbohydrate Recognition Domain

Eijk¹,

White

Crouch

et al. 2003

The Journal of Immunology

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Influenza A virus (IAV) infections are a major cause of respiratory disease of humans and animals. Pigs can serve as important intermediate hosts for transmission of avian IAV strains to humans, and for the generation of reassortant strains; this may result in the appearance of new pandemic IAV strains in humans. We have studied the role of the porcine lung collectins surfactant proteins D and A (pSP-D and pSP-A), two important components of the innate immune response against IAV. Hemagglutination inhibition assays revealed that both pSP-D and pSP-A display substantially greater inhibitory activity against IAV strains isolated from human, swine, and horse, than lung collectins from other animal species. The more potent activity of pSP-D results from interactions mediated by the asparagine-linked oligosaccharide located in the carbohydrate recognition domain of pSP-D, which is absent in SP-Ds from other species characterized to date. Presence of this sialylated oligosaccharide moiety enhances the anti-influenza activity of pSP-D, as demonstrated by assays of viral aggregation, inhibition of infectivity, and neutrophil response to IAV. The greater hemagglutination inhibitory activity of pSP-A is due to porcine-specific structural features of the conserved asparagine-linked oligosaccharide in the carbohydrate recognition domain of SP-A. A more efficient lung collectin-mediated immune response against IAV in pigs may play a role in providing conditions by which pigs can act as “mixing vessel” hosts that can lead to the production of reassortant, pandemic strains of IAV.

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Increased Antiviral and Opsonic Activity of a Highly Multimerized Collectin Chimera

Cited by 29 publications

References 22 publications

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Surfactant Protein D Gene Polymorphism Associated with Severe Respiratory Syncytial Virus Infection

Porcine Pulmonary Collectins Show Distinct Interactions with Influenza A Viruses: Role of theN-Linked Oligosaccharides in the Carbohydrate Recognition Domain

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