Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein

Santos‐López, Gerardo; Scior, Thomas; Borraz-Argüello, María del Tránsito; Vallejo-Ruíz, Verónica; Herrera‐Camacho, Irma; Tapia-Ramı́rez, José; Reyes‐Leyva, Julio

doi:10.1590/s1413-86702009000100007

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…In contrast, numerous microbial pathogens express enzymes that cleave sialic acid (sialidases; also called neuraminidases) (16, 17), such as the viruses causing influenza (18) or mumps (19), the bacterial pathogens Streptococcus pneumoniae (20) and Pseudomonas aeruginosa (21), the fungus Aspergillus fumigatus (22), and the protozoan parasite Trypanosoma cruzi (23). The overall extent of cell surface sialylation has been found to decrease in activated macrophages, neutrophils, B cells, T cells, and natural killer cells (24–28), suggesting that “unmasking” of Siglecs from cis sialic acid engagement occurs during immune activation (27).…”

Section: Introductionmentioning

confidence: 99%

Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase

Chang

Uchiyama

Varki

et al. 2012

mBio

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Cell surface expression of sialic acid has been reported to decrease during immune cell activation, but the significance and regulation of this phenomenon are still being investigated. The major human bacterial pathogen Streptococcus pneumoniae causes pneumonia, sepsis and meningitis, often accompanied by strong inflammatory responses. S. pneumoniae expresses a sialidase (NanA) that contributes to mucosal colonization, platelet clearance, and blood-brain barrier penetration. Using wild-type and isogenic NanA-deficient mutant strains, we showed that S. pneumoniae NanA can desialylate the surface of human THP-1 monocytes, leading to increased ERK phosphorylation, NF-κB activation, and proinflammatory cytokine release. S. pneumoniae NanA expression also stimulates interleukin-8 release and extracellular trap formation from human neutrophils. A mechanistic contribution of unmasking of inhibitory Siglec-5 from cis sialic acid interactions to the proinflammatory effect of NanA is suggested by decreased SHP-2 recruitment to the Siglec-5 intracellular domain and RNA interference studies. Finally, NanA increased production of proinflammatory cytokines in a murine intranasal challenge model of S. pneumoniae pneumonia.Importance Sialic acids decorate the surface of all mammalian cells and play important roles in physiology, development, and evolution. Siglecs are sialic acid-binding receptors on the surface of immune cells, many of which engage in cis interactions with host sialoglycan ligands and dampen inflammatory responses through transduction of inhibitory signals. Recently, certain bacterial pathogens have been shown to suppress leukocyte innate immune responses by molecular mimicry of host sialic acid structures and engagement of inhibitory Siglecs. Our present work shows that the converse can be true, i.e., that a microbial sialic acid-cleaving enzyme can induce proinflammatory responses, which are in part mediated by unmasking of an inhibitory Siglec. We conclude that host leukocytes are poised to detect and respond to microbial sialidase activity with exaggerated inflammatory responses, which could be beneficial or detrimental to the host depending on the site, stage and magnitude of infection.

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Section: Introductionmentioning

confidence: 99%

Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase

Chang

Uchiyama

Varki

et al. 2012

mBio

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“…6d) has specifically been shown to interact with the fusion peptide, and these interactions are essential for its initial folding [25]. Conserved heptad repeats in the HN protein interact with the F protein to aid in membrane fusion [29,30] (Fig. 7b).…”

Section: Discussionmentioning

confidence: 99%

“…A Dunnett post-test was conducted in Prism where p \ 0.05 was considered significant. An asterisk represents a significant fold change over mock at a given timepoint protein of paramyxoviruses [29,30] (Fig. 7b).…”

Section: Phylogenetic Analysismentioning

confidence: 99%

Novel Atlantic bottlenose dolphin parainfluenza virus TtPIV-1 clusters with bovine PIV-3 genotype B strains

et al. 2015

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Parainfluenza virus 3 (PIV-3) is a common viral infection not only in humans, but also in many other species. Serological evidence suggests that nearly 100 % of children in the United States have been infected with PIV-3 by 5 years of age. Similarly, in cattle, PIV-3 is commonly associated with bovine respiratory disease complex. A novel dolphin PIV-3 (TtPIV-1) was described by Nollens et al. in 2008 from a dolphin that was diagnosed with an unknown respiratory illness. At that time, TtPIV-1 was found to be most similar to, but distinct from, bovine PIV-3 (BPIV-3). In the present study, similar viral growth kinetics and pro-inflammatory cytokine (IL-1β, IL-6, and CXCL8) production were seen between BPIV-3 and TtPIV-1 in BEAS-2B, MDBK, and Vero cell lines. Initial nomenclature of TtPIV-1 was based on partial sequence of the fusion and RNA polymerase genes. Based on the similarities we saw with the in vitro work, it was important to examine the TtPIV-1 genome in more detail. Full genome sequencing and subsequent phylogenetic analysis revealed that all six viral genes of TtPIV-1 clustered within the recently described BPIV-3 genotype B strains, and it is proposed that TtPIV-1 be re-classified with BPIV-3 genotype B strains.

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“…Knowing that the HN176 polypeptide is including the region that has been suggested to be involved in the NA activity [33], this activity was measured in total protein extracts. We verified by two methods that the NA activity was present in the pcDNAHN176-transfected cells.…”

Section: Discussionmentioning

confidence: 99%

A 176 amino acid polypeptide derived from the mumps virus HN ectodomain shows immunological and biological properties similar to the HN protein

Herrera¹,

Bárcenas²,

Hernández³

et al. 2010

Virol J

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BackgroundThe hemagglutinin-neuraminidase (HN) protein is the major antigenic determinant of the Mumps virus (MuV) and plays an important role in the viral infectious cycle through its hemagglutination/hemadsorption (HA/HD) and neuraminidase (NA) activities. Objective: analyze the biological and immunological properties of a polypeptide derived from a highly conserved region of the HN ectodomain. Methods: a highly conserved region of the HN gene among several MuV genotypes was chosen to be cloned in a eukaryotic expression vector. The pcDNAHN176-construct was transfected into Vero cells and RNA expression was detected by RT-PCR, while the corresponding polypeptide was detected by immunofluorescence and immunochemistry techniques. The HD and NA activities were also measured. The immunogenic properties of the construct were evaluated using two systems: rabbit immunization to obtain sera for detection of the HN protein and neutralization of MuV infection, and hamster immunization to evaluate protection against MuV infection.ResultsA 567 nucleotide region from the HN gene was amplified and cloned into the plasmid pcDNA3.1. Vero cells transfected with the construct expressed a polypeptide that was recognized by a MuV-hyperimmune serum. The construct-transfected cells showed HD and NA activities. Sera from immunized rabbits in vitro neutralized two different MuV genotypes and also detected both the HN protein and the HN176 polypeptide by western blot. Hamsters immunized with the pcDNAHN176-construct and challenged with MuV showed a mild viral infection in comparison to non-immunized animals, and Th1 and Th2 cytokines were detected in them.ConclusionsThe pcDNAHN176-construct was capable of expressing a polypeptide in Vero cells that was identified by a hyperimmune serum anti Mumps virus, and these cells showed the HD and NA activities of the complete MuV HN protein. The construct also elicited a specific immune response against MuV infection in hamsters.

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Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein

Cited by 19 publications

References 42 publications

Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase

Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase

Novel Atlantic bottlenose dolphin parainfluenza virus TtPIV-1 clusters with bovine PIV-3 genotype B strains

A 176 amino acid polypeptide derived from the mumps virus HN ectodomain shows immunological and biological properties similar to the HN protein

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