Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus

Zanin, Mark; Marathe, Bindumadhav M.; Wong, Sook‐San; Yoon, Sun‐Woo; Collin, Emily A.; Oshansky, Christine M.; Jc, Jones; Hause, Ben M.; Webby, Richard J.

doi:10.1128/jvi.02537-14

Cited by 38 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments in vitro demonstrated that an overlay of human mucus can inhibit the infection of underlying MDCK cells by both swine- and human-origin viruses in vitro , whilst swine mucus does not appear to inhibit infection (Cohen et al, 2013; Zanin et al, 2015) (figure 3a and b). The interaction between influenza viruses and mucus may also be a factor in viral transmissibility, particularly in the context of NA enzymatic activity.…”

Section: Influenza Virusesmentioning

confidence: 99%

“…The interaction between influenza viruses and mucus may also be a factor in viral transmissibility, particularly in the context of NA enzymatic activity. Pandemic H1N1 viruses isolated in swine with almost undetectable NA enzymatic activity were significantly inhibited by mucus in NHBE cell cultures in vitro (Zanin et al, 2015). These viruses did not transmit via aerosols in ferrets and direct contact transmission was severely attenuated (Zanin et al, 2015).…”

Section: Influenza Virusesmentioning

confidence: 99%

“…Pandemic H1N1 viruses isolated in swine with almost undetectable NA enzymatic activity were significantly inhibited by mucus in NHBE cell cultures in vitro (Zanin et al, 2015). These viruses did not transmit via aerosols in ferrets and direct contact transmission was severely attenuated (Zanin et al, 2015). Similarly, viruses expressing NA proteins with short stalks that have decreased enzymatic activity against multivalent substrates such as those found on cells are inhibited by mucus in vitro (Castrucci and Kawaoka, 1993; Matsuoka et al, 2009).…”

Section: Influenza Virusesmentioning

confidence: 99%

See 2 more Smart Citations

The Interaction between Respiratory Pathogens and Mucus

Zanin

Baviskar

Webster

et al. 2016

Cell Host & Microbe

Self Cite

235

228

View full text Add to dashboard Cite

Summary The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus.

show abstract

Section: Influenza Virusesmentioning

confidence: 99%

Section: Influenza Virusesmentioning

confidence: 99%

Section: Influenza Virusesmentioning

confidence: 99%

See 1 more Smart Citation

The Interaction between Respiratory Pathogens and Mucus

Zanin

Baviskar

Webster

et al. 2016

Cell Host & Microbe

Self Cite

235

228

View full text Add to dashboard Cite

show abstract

“…Tight junction proteins are also key components of the epithelial barrier function and integrity that protect against viral infection and potentially influence the susceptibility of tissue to viral infection. Mucin production at mucosal epithelial sites additionally influences virus-host interactions at the epithelial barrier and ultimately impacts viral infection and transmission [5,6,7]. While some of these features may be present in conventional monolayer cell cultures, they often lack the polarity and other topographic features that are present in vivo.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

Gardner

Herbst-Kralovetz

2016

Viruses

View full text Add to dashboard Cite

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.

show abstract

“…While swine to human transmission was observed in both precursor pH1N1 viruses containing the North American-origin NA, no secondary human cases were observed and pre-2009 isolates do not appear to be transmissible to ferrets via respiratory droplets. 28–31 Only after attaining the Eurasian-origin M segment and Eurasian-origin NA, of increased activity and similarity to HA, did the virus become transmissible. 28,32 A comprehensive study by Kobasa et al of N2 viruses isolated from 1957 to 1987 found a time-dependent drift in substrate specificity.…”

mentioning

confidence: 99%

Quantification of Influenza Neuraminidase Activity by Ultra-High Performance Liquid Chromatography and Isotope Dilution Mass Spectrometry

et al. 2017

View full text Add to dashboard Cite

Mounting evidence suggests that neuraminidase’s functionality extends beyond its classical role in influenza virus infection and that antineuraminidase antibodies offer protective immunity. Therefore, a renewed interest in the development of neuraminidase (NA)-specific methods to characterize the glycoprotein and evaluate potential advantages for NA standardization in influenza vaccines has emerged. NA displays sialidase activity by cleaving off the terminal N-acetylneuraminic acid on α-2,3 or α-2,6 sialic acid containing receptors of host cells. The type and distribution of these sialic acid containing receptors is considered to be an important factor in transmission efficiency of influenza viruses between and among host species. Changes in hemagglutinin (HA) binding and NA specificity in reassortant viruses may be related to the emergence of new and potentially dangerous strains of influenza. Current methods to investigate neuraminidase activity use small derivatized sugars that are poor models for natural glycoprotein receptors and do not provide information on the linkage specificity. Here, a novel approach for rapid and accurate quantification of influenza neuraminidase activity is achieved utilizing ultra-high performance liquid chromatography (UPLC) and isotope dilution mass spectrometry (IDMS). Direct LC-MS/MS quantification of NA-released sialic acid provides precise measurement of influenza neuraminidase activity over a range of substrates. The method provides exceptional sensitivity and specificity with a limit of detection of 0.38 μM for sialic acid and the capacity to obtain accurate measurements of specific enzyme activity preference toward α-2,3-sialyllactose linkages, α-2,6-sialyllactose linkages, or whole glycosylated proteins such as fetuin.

show abstract

Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus

Cited by 38 publications

References 39 publications

The Interaction between Respiratory Pathogens and Mucus

The Interaction between Respiratory Pathogens and Mucus

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

Quantification of Influenza Neuraminidase Activity by Ultra-High Performance Liquid Chromatography and Isotope Dilution Mass Spectrometry

Contact Info

Product

Resources

About