New cures for the common cold?

The common cold virus grows best at cooler temperatures (like in your nose), just a few degrees below core body temperature. Why? Because various components of the immune system work better at warm temperatures. Recently, Yale researchers identified two new temperature-dependent host defense strategies that combat the common cold.

The same group already showed that interferon is secreted at 37^oC (98.6^oF, core body temperature) in response to the cold virus - rhinovirus (RV). However, when they inhibited the interferon response, viral replication still depended partially on temperature, suggesting that additional temperature-dependent antiviral activities were at play.
  Ultimately, they showed that, at 37^oC compared to 33^oC, RV-infected cells underwent apoptosis earlier at 37^oC than at the cooler temperature of 33^oC; virus replication also decreased at 37^oC compared to 33^oC. In addition, they showed that the RNA-degrading enzyme RNAseL effectively decreased RV replication at 37^oC versus 33^oC.

To show that apoptosis helped curb viral replication at 37^oC, they overexpressed the anti-apoptotic protein Bcl-2. RV replication increased in cells when Bcl-2 was overexpressed (to inhibit apoptosis).

Since dsRNAs accumulate during RV infection, they reasoned that the RNA-degrading enzyme RNAseL may be expressed at a higher level at 37^oC than 33^oC. This was indeed the case. The level of RNAseL mRNA was 2.2-fold higher at 37^oC than 33^oC. They used siRNA to knockdown RNAseL production in RV-infected cells; RNAseL knockdown increased RV replication at 37^oC compared to when RNaseL was not overexpressed at this temperature..

What’s more, the group found that apoptosis and RNaseL are redundant mechanisms that cells use to control virus replication. To show this, they compared the effects of inhibiting apoptosis and RNAseL simultaneously or separately. In infected control cells, there was a 42-fold difference in peak viral titer at 33^oC versus 37^oC (indicating enhanced viral replication at 33^oC). The difference was 61-fold or 13-fold if RNAseL or apoptosis were inhibited, respectively. However, if both RNAaseL and apoptosis were inhibited simultaneously, there was only a 5-fold difference in peak viral titer.

Overall, these findings reveal new ways to target the common cold, and this is especially important for people who have a weakened immune system or asthma, since the virus can exacerbate symptoms.

Sources: PNAS, Yale, Wikipedia