Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep-Oct;36(5):2357-2364.
doi: 10.21873/invivo.12967.

Epipharyngeal Abrasive Therapy Down-regulates the Expression of Cav1.2: A Key Molecule in Influenza Virus Entry

Kensuke Nishi  1   2   3 , Shohei Yoshimoto  4   5 , Soichiro Nishi  2 , Tatsuro Nishi  2   3 , Ryushiro Nishi  2 , Toshiyuki Tsunoda  6 , Hiromitsu Morita  7 , Hiroaki Tanaka  8 , Osamu Hotta  9 , Susumu Yasumasu  2 , Kenji Hiromatsu  10 , Senji Shirasawa  6 , Takashi Nakagawa  11 , Takafumi Yamano  12
Affiliations

Epipharyngeal Abrasive Therapy Down-regulates the Expression of Cav1.2: A Key Molecule in Influenza Virus Entry

Kensuke Nishi et al. In Vivo. 2022 Sep-Oct.

Abstract

Background/aim: Influenza A virus (IAV) infection causes an inflammatory response to the respiratory mucosa. The viral glycoprotein hemagglutinin (HA) binds to the sialylated voltage-dependent Ca2+ channel (Cav1.2) in ciliated epithelium. The binding of HA and sialylated Cav1.2 is considered essential to IAV infection, entry, and IAV-induced Ca2+ oscillation. The epipharynx comprises the ciliated epithelium, which is the initial target for viruses that cause upper respiratory tract infections. Previously, we showed that epipharyngeal abrasive therapy (EAT), a treatment for chronic epipharyngitis in Japan, which scratches the epipharyngeal mucosa with a cotton swab containing zinc chloride, induces squamous metaplasia. In this study, we evaluated whether squamous metaplasia by EAT affects the expression patterns of Cav1.2.

Patients and methods: The study subjects were seven patients who had not been treated with EAT and 11 patients who had. For the immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of Cav1.2 was described using the immunohistochemical score (IHC score).

Results: The IHC scores for Cav1.2 in the EAT-treated group was 4.19-fold lower than those in the non-treated group (p=0.0034).

Conclusion: EAT down-regulates the expression of Cav1.2, a key cell surface molecule in influenza virus entry via squamous metaplasia. Thus, EAT may be a simple method for preventing influenza infection.

Keywords: Epipharyngeal abrasive therapy (EAT); chronic epipharyngitis; influenza; influenza A virus (IAV); voltage-dependent Ca2+ channel (Cav1.2).

PubMed Disclaimer

Conflict of interest statement

The Authors declare that they have no competing interests in relation to this study.

Figures

Figure 1
Figure 1. The method of epipharyngeal abrasive therapy (EAT). (A) Trans-nasal EAT using a sterile straight nasal cotton swab. (B) Trans-oral EAT using a pharyngeal cotton swab. (C) Endoscopic trans-nasal EAT. The entire epipharyngeal wall is scrubbed using a sterile straight nasal cotton swab soaked in 1% ZnCl2 solution. The white triangle indicates a sterile straight nasal cotton swab.
Figure 2
Figure 2. Protein expression patterns of Cytokeratin 13 (CK13) in patient epipharynx samples of the epipharyngeal abrasive therapytreated and non-treated groups.
Figure 3
Figure 3. α2,6 Sialic acid expression in patient tissue samples without and with epipharyngeal abrasive therapy (EAT). (A) Sialic acid in α2,6 linkage was recognized with biotinylated lectin Sambucus sieboldiana (SSA). (B) Immunohistochemical (IHC) scores for lectin SSA expression on the epipharyngeal mucosa of the EAT-treated (n=11) and non-treated groups (n=7). ns: Not significant.
Figure 4
Figure 4. Protein expression patterns of Cav1.2 in patient tissue samples without and with epipharyngeal abrasive therapy (EAT). (A) Cav1.2 expression in the epipharynx of the EAT-treated and non-treated groups. (B) Immunohistochemical (IHC) scores for Cav1.2 expression on the epipharyngeal mucosa of the EAT-treated (n = 11) and non-treated groups (n = 7). **Significantly different at p<0.01.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Yang J, Li M, Shen X, Liu S. Influenza A virus entry inhibitors targeting the hemagglutinin. Viruses. 2013;5(1):352–373. doi: 10.3390/v5010352. - DOI - PMC - PubMed
    1. Jiang X, Tan M, Xia M, Huang P, Kennedy MA. Intra-species sialic acid polymorphism in humans: a common niche for influenza and coronavirus pandemics. Emerg Microbes Infect. 2021;10(1):1191–1199. doi: 10.1080/22221751.2021.1935329. - DOI - PMC - PubMed
    1. Samji T. Influenza A: understanding the viral life cycle. Yale J Biol Med. 2009;82(4):153–159. - PMC - PubMed
    1. Thompson AJ, Paulson JC. Adaptation of influenza viruses to human airway receptors. J Biol Chem. 2021;296:100017. doi: 10.1074/jbc.REV120.013309. - DOI - PMC - PubMed
    1. Fujioka Y, Nishide S, Ose T, Suzuki T, Kato I, Fukuhara H, Fujioka M, Horiuchi K, Satoh AO, Nepal P, Kashiwagi S, Wang J, Horiguchi M, Sato Y, Paudel S, Nanbo A, Miyazaki T, Hasegawa H, Maenaka K, Ohba Y. A sialylated voltage-dependent Ca2+ channel binds hemagglutinin and mediates influenza A virus entry into mammalian cells. Cell Host Microbe. 2018;23(6):809–818.e5. doi: 10.1016/j.chom.2018.04.015. - DOI - PubMed

MeSH terms

Substances