Human Nose Model Replicates the First Stages of Respiratory Infections

Researchers at Baylor College of Medicine have developed a versatile model of the cells layering the inside of the human nose, which they used to examine  the earliest stages of SARS-CoV-2 and respiratory syncytial virus (RSV) infection. The Baylor nose organoid replicates the first steps of viral infection from airborne diseases and models the complex interactions between human cells and the viruses.

“In the case of respiratory viruses, such as SARS-CoV-2 and RSV, the infection begins in the nose when one breathes in the virus,” says Dr. Pedro Piedra, professor of molecular virology and microbiology, pediatrics and of pharmacology and chemical biology at Baylor. “The human nose organoids we have developed provide access to the inside of the human nose, enabling us to study the early events of the infection in the lab, something we had not had before.”

The side of the organoid exposed to air was comprised of epithelial cells that line the inside of the nose. “Our three-dimensional organoid system replicates this natural situation in the lab using nose epithelium harvested with a nasal swab,” says first author Dr. Anubama Rajan, a postdoctoral associate in the Dr. Piedra’s lab. “We grow the harvested epithelium in tissue culture plates that provide an air-liquid interphase, where the top side of the epithelium is exposed to air and the bottom side is bathed in liquid with nutrients and other factors.”

To study the interaction between SARS-CoV-2 and RSV and the nose epithelium, the researchers simulated a natural infection by placing each virus separately on the air side of the culture plates and studying the changes that occurred on the nose organoid. “We observed divergent responses to SARS-CoV-2 and RSV infection,” says co-author Dr. Vasanthi Avadhanula, assistant professor of molecular virology and microbiology at Baylor. “SARS-CoV-2 induces severe damage to the epithelium, no interferon response (an antiviral first defense response), and minimal mucus secretion. In striking contrast, RSV induces abundant mucus secretion and a profound interferon response.”

The team also used their human nose organoid model of RSV infection to test the efficacy of palivizumab, a therapeutic monoclonal antibody approved by the FDA for preventing severe RSV disease in high-risk infants. The researchers placed palivizumab in the liquid-filled chamber to better model what occurs when therapeutic antibodies enter blood circulation and provide protection of the airways against RSV infection.  “In our model, palivizumab effectively prevented RSV infection in a concentration-dependent manner,” says Avadhanula.

Development of the human nose organoid system is part of a preclinical evaluation of therapies that would help accelerate the transfer of lab-developed therapeutics to the bedside. The organoid system can also reveal new insights into how a person’s initial control of infection occurs and what would make a person more susceptible to a virus than another. This system also can be used to study other respiratory viruses and potentially other disease-causing microbes.

The organoid is described in more detail in a recent issue of the journal mBIO.