Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis

Emily Wasserman, Rika Gomi, Anurag Sharma, Seunghee Hong, Rohan Bareja, Jinghua Gu, Uthra Balaji, Arul Veerappan, Benjamin I. Kim, Wenzhu Wu, Andrea Heras, Jose Perez-Zoghbi, Biin Sung, Seyni Gueye-Ndiaye, Tilla S. Worgall, Stefan Worgall

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serinepalmitoyl transferase (SPT), the rate-limiting enzyme of de novo sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis. Children with asthma and 17q21 asthma risk alleles display decreased sphingolipid synthesis in blood cells. Reduced SPT activity results in airway hyperreactivity, a hallmark feature of asthma. 17q21 asthma risk alleles are also linked to childhood infections with human rhinovirus (RV). This study evaluates the interaction of RV with the de novo sphingolipid synthesis pathway, and the alterative effects of concurrent SPT inhibition in SPT-deficient mice and human airway epithelial cells. In mice, RV infection shifted lung sphingolipid synthesis gene expression to a pattern that resembles genetic SPT deficiency, including decreased expression of Sptssa, a small SPT subunit. This pattern was pronounced in lung epithelial cellular adhesion molecule (EpCAM1) cells and reproduced in human bronchial epithelial cells. RV did not affect Sptssa expression in lung CD451 immune cells. RV increased sphingolipids unique to the de novo synthesis pathway in mouse lung and human airway epithelial cells. Interestingly, these de novo sphingolipid species were reduced in the blood of RV-infected wild-type mice. RV exacerbated SPT deficiency-associated airway hyperreactivity. Airway inflammation was similar in RV-infected wild-type and SPT-deficient mice. This study reveals the effects of RV infection on the de novo sphingolipid synthesis pathway, elucidating a potential mechanistic link between 17q21 asthma risk alleles and rhinoviral infection.

Original languageEnglish
Pages (from-to)302-311
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number3
Publication statusPublished - 2022 Mar

Bibliographical note

Funding Information:
Supported by the National Institute of Allergy and Infectious Diseases grant R21/AI140724-01 (S.W.) and the generous support of Ronay Menschel, Christine and Pasco Alfaro, and Joanna Weiss. E.W. was supported by the National Center for Advancing Translational Sciences of the NIH (KL2/TR0002385-01).

Publisher Copyright:
© 2022 American Thoracic Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis'. Together they form a unique fingerprint.

Cite this