Human nose model shows SARS-CoV-2 and RSV infection

Preclinical models that recreate aspects of human airway disease are essential to the advancement of new therapies and vaccines.In the current study published in the journal mBIOResearchers at Baylor College of Medicine have reported the development of a versatile human nasal organoid. This is a laboratory representation of cells that layer the inside of the nose where the first event of a natural viral infection occurs.

The team used a nasal organoid that models the complex interaction between human cells and the virus to infect with SARS-CoV-2, the virus that causes COVID-19, and the major respiratory syncytial virus (RSV). Showed an important difference from infection by virus. Pediatric respiratory virus provides a better understanding of the first steps to the disease and leads to potential new treatments.

This model has also proven to be a useful tool for testing the efficacy of treatments such as the FDA-approved monoclonal antibody palivizumab to prevent severe RSV disease in high-risk infants. rice field. The human nasal organoid system is part of a preclinical evaluation of therapies developed in the laboratory that help accelerate the transition to bedside.

“In the case of respiratory viruses such as SARS-CoV-2 and RSV, the infection begins in the nose when the virus is inhaled,” the corresponding author said. Dr. Pedro Piedra,Professor Molecular virology and microbiology, Pediatrics With Pharmacology and chemical biology At Baylor. He is also the director of Baylor’s Laboratory for Clinical Laboratory Improvement and Correction (CLIA) Certified Respiratory Virus Diagnostic Institute. “The human nasal organoids we have developed provide access to the inside of the human nose, making it possible to study unprecedented early events of infection in the laboratory. We have succeeded in developing human nasal organoids from both adults and infants. “

The cells inside the nose, which line the epithelium, are exposed to the air on one side and the blood circulation system on the other.
“Our 3D organic system uses nasal epithelium taken with a nasal swab to recreate this natural situation in the laboratory,” the lead author explained. Dr. Anuba Marajan, Postdoctoral fellow in Piedra Lab. “The collected epithelium is grown on a tissue culture plate that provides an interphase. During this period, the upper surface of the epithelium is exposed to air and the lower surface is immersed in a liquid containing nutrients and other factors.”
To study the interaction of SARS-CoV-2 or RSV with the nasal epithelium, researchers placed each virus separately on the air side of the culture plate and studied the changes that occurred in the nasal organoids. , Simulated a natural infection.

“We have observed different reactions to SARS-CoV-2 and RSV infection,” the co-authors said. Dr. Vasanthi Avadhanula, Associate Professor of Molecular Virology and Microbiology at Baylor University. “SARS-CoV-2 causes severe damage to the epithelium, has no interferon response (the first antiviral defense response), and minimizes mucus secretion. In contrast, RSV is rich in mucus. Induces secretion and profound interferon response. “

The team also tested the efficacy of palivizumab using a human nasal organoid model of RSV infection. In this case, they placed the therapeutic monoclonal antibody in a chamber filled with liquid, and the therapeutic antibody entered the blood circulation, closer to the human experience of providing airway protection against RSV infection.

“In our model, palivizumab effectively prevented RSV infection in a concentration-dependent manner,” said Avadhanula, co-director of the (CLIA) Certified Respiratory Virus Diagnosis Institute and the Institute’s research program. increase.

In this study, for the first time, the team described a non-invasive, reproducible, and reliable approach to establishing human nasal organoids that enable long-term research. Previous models were created using invasive lung or nasal biopsy or bronchoalveolar lavage. “The availability of nasal swab samples facilitates non-invasive approaches in the general adult and vulnerable pediatric populations,” said Piedra.

Another benefit of using this new human nasal organoid system is that it reveals how the initial control of a person’s infection takes place and makes one more susceptible to the virus than others. Being able to provide insights. This system can also be used to study microorganisms that cause other respiratory viruses and potentially other illnesses.

Other contributors to this work include Ashley Morgan Weaver, Gina Marie Aloisio, Joseph Gerinsky, Hannah L. Johnson, Susan F. Venable, Trevor McBride, Leticia Eideyan, Felipe Andres Piedra, Kunyanje, Ernestiname. Rikov Portillo, Marilla Macantier Miri, Xi-Lei Zeng, Michael A. Mancini, Fabio Stossi, Anthony W. Maresso, Shalaka A. Kotkar, Mary K. Estes, Sarah Blutt, all Baylor College of Medicine.

This work is supported by Public Health Services Grants P30DK056338, NIH Grants (DK56338, CA125123, ES030285, T32AI055413, U19 AI144297, and U19 Al116497), Texas Cancer Prevention Institute (CPRIT; RP150578, RP170719), Dan L. Duncan Comprehensive. it was done. Cancer Center and John S. Dan Gulf Coast Chemistry Genomics Consortium.