Our new manuscript is up online at PLOS Pathogens:
Albe, J.R., H.M. Ma, T.G. Gilliland, C.M. McMillen, C.L. Gardner, D.A. Boyles, E.L. Cottle, M.D. Dunn, J. Lundy, K.J. O’Malley, N. Salama, A.W. Walters, I. Vasile-Pandrea, T. Teichert, W.B. Klimstra, D.S. Reed, and A.L. Hartman. In press. Physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in macaques. PLOS Pathogens. Accepted 1/12/21. Available online: https://doi.org/10.1371/journal.ppat.1009308.
This figure shows the different subsets of immune cells present in the brains of EEEV-infected animals compared to controls (gray bars). Not that some cell types remain elevated in surviving animals (blue bars in panel B).
Take home message: The goal of a study like this is to better understand the pathophysiology of disease, so that these parameters can be used in vaccine and therapeutic as markers of efficacy. For instance, if we understand how brain waves, intracranial pressure, cytokines, and cell infiltration change as a result of disease, we can measure these parameters in treated/vaccinated animals. A reduction or amelioration of the changes can be used as a statistical measurement of efficacy. In this case, we were surprised to find residual viral RNA and immune cell infiltrate in the brains of surviving animals, because these animals seem otherwise healthy and we did not appreciate that EEEV may still be reaching the brain in survivors. Further studies will reveal whether EEEV actually penetrates the brain of survivors.