A study in mice finds that the timing of an infection relative to circadian rhythms affects how quickly a virus takes hold.
By Nathan Collins
(Photo: Elena Gurzhiy/Flickr)
Circadian rhythms have a powerful influence on our bodies. They play a role in regulating sleep, body temperature, and other key physiological processes. Abnormal rhythms have been tied to depression, obesity, and seasonal affective disorder. Now, researchers report in Proceedings of the National Academy of Science they’ve found circadian rhythms can affect the progress of disease as well: In mice at least, getting infected just before bedtime drastically increases a virus’ spread.
Cambridge University scientists Rachel Edgar, Akhilesh Reddy, and their colleagues reached that conclusion with the aid of lab mice and a version of herpesvirus, Murid Herpesvirus 4. First, the team dropped a bit of the virus into each mouse’s nose, either just before bedtime or just after waking up. (Mice are nocturnal, so “bedtime” for lab mice corresponds to turning the lights on.) Then, they tracked how the virus spread over the next several weeks.
The results: Herpesvirus spread much faster in the mice infected at bedtime, and the virus peaked at a much higher level—at its maximum, there were 10 times as many copies of the herpesvirus in mice infected at bedtime, compared to the peak infection level in mice infected after they woke up.
Herpesvirus spread much faster in the mice infected at bedtime.
The next question was why circadian clocks were so important. To answer that, the team used a group of mice genetically modified to suppress a gene, called Bmal1, which plays a key role in regulating the mice’s internal clocks—expression of the gene peaks several hours before bedtime, then tapers off until mice wake up again. In mice with suppressed Bmal1, the timing of the herpes infection made no difference, and the peak severity of the infection was about the same as in ordinary mice infected at bedtime. The team replicated those experiments with herpes simplex virus 1 and, using mouse cells rather than live mice, with influenza A, indicating that the effect was not limited to one particular virus or family of viruses.
Further experiments showed that herpesvirus actually boosted Bmal1 operation about six hours after infection, suggesting that the virus could directly disrupt circadian rhythms if the infection was timed right.
“Our results show that altering only the time when hosts are infected significantly affects the extent of virus infection and dissemination in vivo, reflecting the profound change in physiology that naturally occurs over a day,” Edgar, Reddy, and their colleagues write. Down the road, “manipulation of the molecular circadian clockwork may provide a strategy for the development of novel antiviral therapies.”
