Interaction between pollen proteases and ACE2 receptor of SARS-CoV-2

Overview

Pollen allergy is a common seasonal respiratory disease triggered by hypersensitivity to pollen affecting 10-30% of adults and 40% of children, and is a predisposing factor for asthma. Pollens interact with airway epithelium to both stimulate innate immunity and elicit an adaptive immune response.

Proteolytic activity is one route that stimulates release of alarmins and pro-inflammatory cytokines from mucosal epithelia. Previous studies have found the expression of Serine/Cysteine (Ser/Cys) proteases in some types of grass pollen grains, but it is not clear whether there occur in subtropical Bahia or Johnson grass pollen.

Better understanding of the interaction between subtropical grass pollen and airway epithelium may provide insight into interaction between grass pollen grains and certain infectious agents including SARS CoV 2. This virus is an enveloped RNA virus being surrounded by Spike (S) proteins on its surface which contribute to viral entry. The S1 subunit encompasses the receptor-binding domain (RBD) and the S2 subunit includes the fusion peptide. After binding to angiotensin-converting enzyme 2 (ACE-2) receptor by the RBD of S1, the fusion peptide is processed by transmembrane protease serine 2 (TMPRSS2).

Evidence suggests that the inhibition of Ser/Cys proteases in vitro reduces SARS-CoV-2 viral infectivity. Presence of allergen encoded proteases may influence the interaction of respiratory viruses with mucosal epithelial cells. Separately it was found that there might be a positive relationship between pollen concentration and the number of COVID-19 positive cases in different countries.

Hypothesis/Aims

The presence of serine/cysteine proteases of Bahia grass pollen interact with ACE2 receptors affecting binding for S proteins on coronaviruses. Grass pollen proteins induce epithelial cell innate immunity to allergen that counter regulates innate response to respiratory viruses.

References

• Bergougnan et al. Physical and immunological barrier of human primary nasal epithelial cells from non-allergic and allergic donors. World Allergy Organization Journal. 2020;13(3):100109.
• Gilles et al. Pollen exposure weakens innate defense against respiratory viruses. Allergy. 2020;75(3):576-87.
• Skevaki C, Karsonova A, Karaulov A, Xie M, Renz H. Asthma-associated risk for COVID-19 development. Journal of Allergy and Clinical Immunology. 2020;146(6):1295-301.
• Wark et al. ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma. Respirology. 2021
• Zhu et al. Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells.

Research activities

You will start with the collection of fresh Bahia grass pollen outdoor. Then, total RNA will be extracted from the collected pollens to enable analysis of Bahia grass pollen transcriptome for the presence of encoded proteases. Further, the role of pollen proteins in influencing ACE2 structure and inducing innate immunity in human nasal epithelial cultures will be examined

Skills and experience

Students with a background in infection and immunity and an interest in molecular biology will be suited to this project. You will be invited to join the multidisciplinary QUT Allergy Research Group that is funded by ARC as well as government and competitive foundation grants

Scholarships

You may be eligible to apply for a research scholarship.

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Keywords

• ACE2 receptors
• pollen allergy
• hypersensitivity
• immune response

Contact

Contact the supervisor for more information.