How does temperature affect host responses to SARS-CoV-2 and IAV infection in human nasal epithelial cells?

*Important note: bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, directing clinical practice/health-related behaviour, or treated as hard information.

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) are current threats to human health worldwide, little is known about how their infection is modified by environmental factors. A new preliminary edition examines the response to these pathogens in the nose, the primary gateway of entry for both.

Study: Early transcriptional responses of human nasal epithelial cells to infection with influenza A virus and SARS-CoV-2 are different and affected by physiological temperature.  Image credit: pinkeyes/
Stady: Early transcriptional responses of human nasal epithelial cells to infection with influenza A virus and SARS-CoV-2 are different and affected by physiological temperature.. Image credit: pinkeyes/


IAV affects about 8% of the US population annually, while more than 6.6 million people have died of coronavirus disease 2019 (COVID-19) after infection with SARS-CoV-2 worldwide. Both infections can cause severe illness, especially in older and frail patients.

Immune cells first encounter respiratory pathogens in the epithelium of the respiratory tract. A small study examined differences in epithelial cell types and temperatures in the upper versus lower respiratory tract (URT and LRT, respectively).

The normal temperature for a URT is around 33aC vs. 37aC in LRT. Fever may cause it to go up to a maximum of 39aHigh temperatures after infection with rhinoviruses have been shown to stimulate antiviral responses, preventing virus replication at 37aC in mice but not in human cultures.

IAV infects airway and alveolar epithelial cells using sialic acid receptors, mostly on ciliated cells. These are fewer in the lower respiratory tract, and thus, IAV infects type I pneumoniae cells in the lungs additionally.

SARS-CoV-2 infects goblet and ciliated cells using the angiotensin-converting enzyme 2 (ACE2) receptor, although other proteases are also essential.

Acute IAV infection is associated with a lower response to antivirals, interferon impairment, and increased inflammation, leading to lung infection. With SARS-CoV-2, the severity of inflammation is usually lower compared to IAV.

The current study is available on a preprint server bioRxiv*to relate the effect of temperature on host immune responses in cultures mimicking human nasal epithelium.

What does the study show?

The study demonstrates the effect of temperature on viral reproductive fitness as well as the host response to the virus. Second, the researchers found that cultures infected with SARS-CoV-2 showed a delayed transcriptional response compared to IAV.

at a temperature of 37aC, SARS-CoV-2 showed faster replication initially, compared with 33aC. at lower temperature replicated slower than IAV, which showed similar replication at both temperatures.

After IAV infection, nasal epithelial cells (NECs) produced interferons, cytokines, and chemokines belonging to inflammatory or innate immune pathways at higher levels compared to SARS-CoV-2 infection. The higher the fever, the more these cytokines are produced.

The inflammatory cytokine response with SARS-CoV-2 was significantly lower in all viral loads compared with IAV, except for late infected cells at high temperatures. at 37aC and SARS-CoV-2-infected cells showed little difference in transcriptional profile from mock-infected cells.

This refers toWeakened or delayed innate immune responseto SARS-CoV-2 within NECs. The question remains whether this indicates an actual suppression of the immune response or a delay in the induction of immune pathways.

However, such a delay helps explain why SARS-CoV-2 infection is associated with a more severe clinical profile than IAV since inadequate responses to interferon are associated with a higher risk of severe disease. Previous research has often demonstrated the ability of SARS-CoV-2 to inhibit interferon signaling pathways.

The temperature and type of virus affect the host’s response to infection. at 33aThey were C cells, strongly keratinized, with some keratinocytes usually prevalent in the tongue and palate. This may mean that the respiratory system differentiates in part in response to temperature cues.

Another explanation is that keratinization, which is important in wound healing, may show the ability of these cells to persist and recover from injury caused by viral infection faster.

Therefore, lower temperatures and SARS-CoV-2 infection are associated with slower responses to infection. at 37aC, the host infection response slowly becomes perceptible but can be driven by host signals such as damage-associated molecular patterns (DAMPs) rather than pathogen-associated molecular patterns (PAMPs).

With IAV, the same amount of infectious virus was produced over time at either temperature, but the host response was different, seen most clearly at 96 hours post infection (HPI). This contrasts with other studies showing innate responses associated with burden or viral load It needs further verification.

These data indicate that physiological temperature ranges must be considered when evaluating host responses to infection. “

With IAV, pathways related to transmembrane and cell signaling become active after infection. This was not the case for SARS-CoV-2 infection, which resulted in transcriptional pathways related to cytoskeleton and cellular projections.

Perhaps this can be explained in part by the recent finding that the latter uses epithelial cell microvilli and cilia to facilitate infection and spread to neighboring cells, while IAV uses transmembrane transport systems for host cell entry and reproduction. These insights can help identify other host factors necessary for infection, and provide other potential therapeutic or preventive targets.

Previous studies have shown that not all SARS-CoV-2 variants show the same temperature sensitivity, with the ancestral and delta variants being most sensitive to lower temperatures. These have been found to infect lung cells rather than URT cells, in contrast to Omicron, which is less sensitive and targets the URT.

Mutations in IAV also affect some cellular proteins that can affect temperature sensitivity. The proteins affecting this property in both viruses could provide attractive targets for intervention.

Both viruses showed a common set of differentially regulated genes (DRGs) that are involved in host immune response, membrane fusion, and genomic defence. These common target genes could help treat both infections more effectively, especially since the immune pathways are temperature independent.

While the baseline response to antivirals at different temperatures remains consistent, there may be metabolic or signaling changes that affect how well the cultures can adapt to novel stresses such as infection.. “

SARS-CoV-2 has been shown to replicate less efficiently at higher temperatures in an interferon-independent manner. More research will be needed to show whether this common response occurs with all viruses that attack the respiratory tract and different host proteins involved in regulating virus replication at different temperatures.

What are the effects?

Taken together, these data suggest that temperature should be considered when evaluating human pathogens and can help define new treatment strategies as well as understand the basic biology underlying respiratory virus infection of epithelial cells.. “

*Important note: bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, directing clinical practice/health-related behaviour, or treated as hard information.

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