While we’ve all heard the tired warning to wear our coats outside so we don’t get sick, it’s fair to wonder how much validity there is to such reasoning. Are we really more likely to catch a cold in colder weather?
Lucky for us, scientists at Yale are looking into it. Their recent article1, published in Proceedings of the National Academy of Sciences, looked at the effect that colder temperatures had on rhinovirus growth in mouse airway epithelial cells (AECs). It was already known that rhinoviruses grow better at cooler temperatures — around 33 degrees Celsius — but the mechanisms by which this preferential growth occurred remained largely unknown. However, in this article, scientists presented new findings that suggest the mechanism is more related to impaired immune function in the infected cells than directly virus intrinsic.
Specifically, the researchers used ex vivo treatment of mouse AECs infected with a mouse-adapted rhinovirus to test differences in cellular processes at varying temperatures.
When compared to those cells grown at 37 degrees Celsius, the cells grown at 33 degrees Celsius had a significantly decreased amount of immune response elements, including both type 1 and type 3 interferon subtypes and interferon-stimulated genes.
Intriguingly, it is known that interferons limit viral growth and have been specifically reported to limit rhinovirus growth2, and interferon-stimulated genes are known to aid in immune response to viruses.
Taken together, these findings provide a potential mechanism by which growth of rhinovirus might be inhibited at higher temperatures. The paper goes on to further elucidate cellular mechanisms for this differential interferon production. Specifically, the researchers discovered that the recognition of viral replication intermediates, namely, dsRNA, by RIG-I-like receptors (RLRs), was responsible for the increased interferon response at higher temperatures. RLRs are part of our innate immune system and are responsible for recognition of “nonself” antigens, such as viral RNA.
But how is the temperature difference affecting the interferon response? Through a series of experiments, the researchers identified two mechanisms that affect viral growth at differing temperatures. Essentially, they found that at 33 degrees Celsius, decreased RLR enzyme activity was responsible for the less potent interferon response. At 37 degrees Celsius, enhanced signaling through type 1 interferon receptors resulted in increased interferon production.
The the authors’ findings suggest there is a temperature-based growth advantage in cells infected with rhinovirus, and this advantage is mediated through cell-intrinsic mechanisms. While more research is needed, this study could help explain why cold temperatures could lead to more cases of the cold virus.
1 Foxman EF, et al. (2015) Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proc Natl Acad Sci USA [Epub ahead of print].
2 Becker TM, et al. (2013) Exogenous interferons reduce rhinovirus replication and alter airway inflammatory responses. Ann Allergy Asthma Immunol 111(5):397–401.