To design a quantitative system of fatigue that overcomes these two problems, we focused on the phenomenon of labial herpes
, which commonly occurs when fatigue accumulates. Labial herpes is caused by the reactivation of the herpes simplex virus (HSV-1) in response to fatigue. Therefore It can be an objective symptom of excessive fatigue. However, since the ratio of people who own herpes labialis caused by HSV-1 is not high, we judged that it is an inappropriate choice as a biomarker. Therefore, we changed our research target to alternative candidates, Human herpesvirus-6 (HHV-6)
and HHV-7, which have been reported to reactivate in saliva in response to the accumulation of fatigue. In particular, HHV-6 is known to infect 90% of the population in childhood and has the characteristic that it can remain latent in the human body for a lifetime. It has also been reported that fatigue over a period of about a week reactivates the virus and is detected in saliva.
HHV-7 also has been reported to be reactivated in saliva by an accumulation of fatigue. HHV-7 is frequently reactivated in the body, whereas HHV-6 under normal conditions is in a state of complete latent infection and no virus is produced. In addition, HHV-7 is more susceptible to immunity because the virus, once reactivated in the body, is released in saliva. On the other hand, HHV-6 reactivates quickly into saliva without being affected by immunity and is therefore considered to be less susceptible to immunity.
We chose HHV-6 as a biomarker to quantify fatigue since it is considered to be more reproducible in measurement than existing biomarkers.
To construct a system that can be handled without specialized knowledge or skills, we designed a quantification method using CRISPR-Cas12a. This method is more simple than real-time qPCR, which is a method used for quantification of HHV-6 commonly, and does not require specialized knowledge, and thus offers new possibilities for applications in determining fatigue accumulation. In addition, this Cas protein-based quantification method can be used to check the results more quickly than real-time qPCR and does not require special equipment, so it is a system with lower hurdles for social implementation.