Why SARS-CoV-2 replicates better in the upper respiratory tract

“SARS-CoV-2 and SARS-CoV are genetically very similar, producing a homologous repertoire of viral proteins and using the same receptors to infect human cells, but these similarities. Nevertheless, there are also important differences between the two viruses, “says Ronald Dyckman of the Institute for Infectious Diseases (IFIK) at the University of Bern. For example, SARS-CoV infections are characterized by severe disease and inflammation of the lower respiratory tract, and infected individuals are transmitted only after the onset of symptoms, making it easier to identify and interrupt the infection chain.

In contrast, SARS-CoV-2 preferentially replicates in the upper respiratory tract (nasal cavity, pharynx, trachea) and can be efficiently transmitted from one individual to another before symptoms of the disease appear. .. In addition, the outcome of SARS-CoV-2 infection varies widely from person to person and can manifest itself as asymptomatic, mild, or severe disease. Elderly people and people with certain underlying illnesses (heart disease, diabetes, cancer) are at increased risk of developing serious illnesses that are often associated with infection of lower respiratory tract tissue, high levels of inflammation, and lung failure. I will.

Temperature is important

To better understand why SARS-CoV and SARS-CoV-2 infections lead to these different clinical outcomes, researchers at the University of Bern have used specialized human airway cell cultures to use SARS-CoV. And the effect of airway temperature on SARS-CoV was investigated. -2 replication. The cells are derived from human samples and mimic the cellular complexity found in the respiratory tract. They grow in special containers, are nourished from below and exposed to air on the top, like cells in the human trachea. Culture also makes mucus and has cilia that beat very quickly. “The composition of these cells is so similar to the cells found in human tissue that it is a related system that can be used in the laboratory to study respiratory viruses,” explains Dykeman.

Researchers are now using this existing model for the first time to study the effects of respiratory temperature on SARS-CoV and SARS-CoV-2 replication. They found that temperature plays an important role because SARS-CoV-2 prefers to replicate at the temperatures normally found in the upper respiratory tract (33 ° C). Due to the low incubation temperature, the virus replicated faster and more sophisticated than when infected at 37 ° C to mimic the environment in the lower lungs. Unlike SARS-CoV-2, SARS-CoV replication was unaffected by different incubation temperatures. The experiments were conducted at both the IVI Institute for High Security Security in Mitterhausan and the Institute for Biosafety at the Institute for Infectious Diseases (IFIK) at the University of Bern. ..

Temperature also affects the response from the epithelium

The team also analyzed which genes are turned on and off after SARS-CoV and SARS-CoV-2 infection, how cells in the human respiratory tract respond to infection and which innate immune programs are activated. I understood what would be done. The innate immune system is our body’s “first line of defense” against invading pathogens and is important not only to contain invaders, but also to teach them how to respond appropriately to other branches of the immune system. is.

When mimicking the condition seen in the upper respiratory tract (33 ° C), the team found that SARS-CoV-2 infection was as strong as when mimicking the condition seen in the lower respiratory tract, producing an innate immune response in these cells. I found it not irritating. Tube (37 ° C). “This may help explain why SARS-CoV-2 replicates more efficiently at low temperatures, as the strength of the innate immune response can directly affect the degree of viral replication. There is, “says Dijkman. It is generally beneficial to initiate a strong innate immune response to the virus, but it is important to note that innate immune responses can be overactivated in some cases. This can be harmful to infected individuals, as high levels of inflammation can induce tissue damage and accelerate the progression of the disease. This is a common phenomenon in patients suffering from severe COVID 19.

“A detailed analysis of SARS-CoV-2 replication and temperature-induced changes in the host’s innate immune defense mechanism helps explain why SARS-CoV-2 replicates so well in the upper respiratory tract, perhaps SARS. -The reason is CoV-2. It is more human-to-human infectious than SARS-CoV, “explains Dykeman.

Important knowledge to fight coronavirus infection

The use of this authentic cell culture model in a controlled laboratory environment has proven to accurately reflect the different behaviors of two similar viruses in a pandemic situation. “This unique system provides insight into the molecular battles that occur between the virus and the host during infection, and subtle changes in the virus-host microenvironment that can affect virus replication and proliferation. We emphasize the importance of the virus, “says Dijkman. Understanding which key players are involved in this process and whether they support the host or virus is a new drug that helps establish highly targeted intervention strategies and combat coronavirus infections. It opens up new opportunities for the development of compounds.