Last Month's Most Accessed Feature: Influenza A proteins: Individual proteome variations

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  • Published: Dec 1, 2017
  • Categories: Proteomics & Genomics / Proteomics
thumbnail image: Last Month's Most Accessed Feature: Influenza A proteins: Individual proteome variations

Influenza factors

Scientists in the US have shown that the proteomes of normal human bronchial epithelial cells are unique for individual people and also respond to infection by the influenza A virus in different ways, findings which could be used to identify people more susceptible to the disease.

Infection by the influenza A virus follows a complex but well-defined path involving a number of different stages and bodily proteins. Many proteins support viral incorporation and replication and these so-called proviral factors, which perform normal cell functions in the absence of infection, can be used in drug discovery programs. They can also be examined to try and reveal the factors behind the severity of the disease.

Scientists working for the FDA in Silver Spring, MD, have been working on the influenza virus and noted that a number of studies have identified different proviral factors, depending on their approach to the problem, but one area that appears to have been overlooked is the potential variation between the proteins from different people. Any differences might help to explain why some people are more susceptible than others to infection by influenza A.

So, Samuel Mindaye, Maryna Eichelberger and colleagues from the Divisions of Viral Products, Biotechnology Research and Review II, and Cellular and Gene Therapies undertook their own proteomics study. They grew normal human bronchial epithelial cells from three donors at an air-liquid interface to mimic conditions in the bronchioles in the lungs where the virus attacks then compared the proteins and their abundances before and after infection with influenza A strain A/H1N1pdm.

Inter-individual proteome variations

The proteins were harvested from each culture and the peptides produced by conventional digestion with trypsin were identified by LC/MS using a hybrid ion mobility/time-of-flight mass spectrometer. Separation on the liquid chromatography column, followed by two more separations stages based on drift time and time of flight ensured good resolution.

The peptide precursor and product ions were searched against the SwissProt human database as well as an in-house database of all proteins from this viral strain. The relative protein abundances were estimated by a label-free method based on the intensity of an added reference protein, bovine catalase.

The number of proteins varied markedly between the three individuals before infection, totalling 1781, 1240 and 890 for donors 1, 2 and 3. Only 24% of them were shared across all three people, indicating that the proteomes are uniquely individual. Those factors from D2 that support viral replication were present at higher levels than in the two other subjects but others that destabilise viral proteins were found at lower concentrations compared with D1 and D3.

Proviral and antiviral protein balance

The cultures were tested several times over 48 hours after infection and the viral proteins from D2 were more abundant than in D1 and D3, which was expected given the higher levels of proviral proteins pre-infection. Higher virus titres were measured in D2 compared with D3.

However, the virus titres of D1 and D2 were comparable, suggesting that there is another factor at play. Given that virus replication was inversely related to the levels of antiviral proteins, the researchers proposed that virus production is governed by a combination of proviral proteins and the antiviral factors.

The unique protein profiles of the three subjects and their responses to influenza A infection suggests that measurement of the proviral and antiviral factors could be carried out on individual people to try and identify those more susceptible to severe influenza. “Together with a full genetic analysis of a large number of donors, this may facilitate identification of genes associated with influenza susceptibility,” the team concluded.

The logical next step would be to carry out large-scale proteome analysis of many more people, including those who are known to be more susceptible to influenza, to confirm the results of the current study.

Related Links

Journal of Proteome Research 2017, 16, 3287-3297: "Impact of Influenza A Virus Infection on the Proteomes of Human Bronchoepithelial Cells from Different Donors"

Article by Steve Down

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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