Thearticle I reviewed was entitled ‘InfluenzaA penetrates host mucus by cleaving sialic acids with neuraminidase.’In their study Miriam Cohen et al. 2013, used frozen bronchus/humantrachea tissue parts, human salivary mucins (HSM) (bead boundpurified) and porcine submaxillary mucins (PSM) to test IAVinteraction with secreted mucus. Previous research have found that,Influenza A virus (IAV) neuraminidase (NA) cleave sialic acids (Sias)from glycans. In addition, these studies found that when NA isinhibited with oseltamivir, it controls viral release and viralinfection of epithelial cells in the human airway. Sialylation andmucin glycosylation differs from species to species that influencesthe influenza specificity in the given host. Mucus has been found tocarry vast variable receptors and as such mucin sialylation createssites similar to target receptor’s cells. Previous research studieshave only studied the binding properties of IAV without consideringmucin secretion despite the known fact that all natural infectionssites have vast cover of secreted sialoglycoprotein (Cohen et al.2013).
AccordingCohen et al. 2013, NA releases virions which cleave Sias fromglycoconjugates on progeny virions and infected cells. Therespiratory epithelia cells secrete mucus which forms a layer ofheavy sialylated glycoproteins which inhibit the entry of viralinfections by assuming the role of sialylated receptors. Researchfindings suggest that NA facilitates influenza penetration in themucus through cleaving sialylated decoys although the mechanisms bywhich this happens have not been ascertained.
Inthis study, the researchers wanted to investigate how IAV interactswith secreted
mucinand thereafter provide evidence on the NA role in early infection ofmucous tissues. Similarly they also needed to demonstrate thedependency of Sia with IAV binding on the musins using the frozenhuman trachea. Their goal was to present invitroevidence that underlying cells in the bronchus/ human trachea couldbe protected from infection by secreted mucus through sialylateddecoys (hemagglutinin, HA) and NA cleavage. In order to achieve this goal, the researchers in this study used purified mucus from twohosts pig and human being to ascertain the binding and cleavageeffect of sialylated human mucus by IAV NA and HA (Cohen et al.2013).
Aftertesting the IAV interaction with mucus, the researchers found that
IAVbonded with the secreted mucus of the frozen bronchustissues/trachea. The IAV depended on binding factor and host type ofHA. Furthermore, the researchers unearthed that, when Sias is removedfrom the tissues through enzymatic cleavage of Arthrobacterureafaciens sialidaselowers the binding capacity of the virus on the mucus this confirmedthe specificity binding aspect of virus to sialylated receptors. Theinhibition of HSM in IAV disease was found to be dependent on Siadose but for PSM it was found that it could not inhibit infections onthe underlying cells of the human trachea. However, HSM was found tocompetitively control NA cleavage in the 4MU-Neu5Ac (Cohen et al.2013).
Inconclusions, the researchers assessed that, IAV interacts with humanmucus on the bronchus tissues and inhibiting IAV infection bysialylated human mucus depends on the dose. In addition, theresearchers found that IAV infection was enhanced when oseltamivirwas used to inhibit NA this in turn facilitates NA cleaving ofsialylated decoys in the early stages of virus infection. It wasapparent from this article that, the sialylated mucin from the hostbody was critical in enhancing protection against IAV infection.Similarly, the findings in the study indicate that the composition ofSia, its density and presentation are vital in controlling the IAVvirus (Cohen et al. 2013).
Theresults of this study experiment are worthy in explaining how IAVinteracts
withsecreted mucus in the human airway epithelial cells as well as how toinhibit IAV infection. However, there are many questions one couldask from this study. One is that, since the study relied on humanspecimens for research, would these findings apply to the differenttypes of influenza infections in the human body? The study focusedon IAV infection on the trachea tissues, what would be the scenarioof these virus interactions with other molecules in the wholerespiratory system the nasal passage and the lungs? Would HSM andPSM inhibit all strains of IAV? My experiment would involve morestudy trials on different animal species and various parts of therespiratory system to understand the interaction of IAV and mucussecretion, and the HSM, PSM inhibition of IAV disease. Particularly,the study would tests healthy and infected mammals in order to get abroad picture of the IAV disease, body reaction (mucus secretion) HSMand PSM inhibitors.
Thenext part of my experiment would focus on possible IAV interactionswith complex molecules in the surrounding human body cells or organs‘ecosystem’ as a way of understanding sialylated hosts musins. Inthis case the experiment would focus on the interaction of IAV withother human body cells like the lungs, brains and thyroid glands.This would involve collecting tissues from healthy mammals lungs,trachea and nose passage. Influenza A virus (IVA) would then beintroduced in the mucus layer of these specimens in order tounderstand the interaction of IVA on different species. The datawould then be graphed to assess the level of interaction andinhibition of IAV in different animal species and parts. This wouldbe achieved by grouping each part with its species i.e. lung tissuein Chimpanzees and the interaction of IAV, HSM and PSM
Cohenet al. 2013, ‘InfluenzaA penetrates host mucus by cleaving sialic acids with
neuraminidase’. Virology Journal 10:321. Retrieved from