Preliminary Studies on Immune Response and Viral Pathogenesis of Zika Virus in Rhesus Macaques

Zika Virus (ZIKV) is primarily transmitted through mosquito bites. It can also be transmitted during sexual intercourse and in utero from mother to fetus. To gain preliminary insight into ZIKV pathology and immune responses on route of transmission, rhesus macaques (RMs) were inoculated with ZIKV (PRVABC59) via intravaginal (IVAG) (n = 3) or subcutaneous (sub Q) (n = 2) routes. Systemic ZIKV infection was observed in all RMs, regardless of the route of inoculation. After 9 days postinfection (dpi), ZIKV was not detected in the plasma of IVAG- and sub-Q-inoculated RMs. Importantly, RMs harbored ZIKV up to 60 dpi in various anatomical locations. Of note, ZIKV was also present in several regions of the brain, including the caudate nucleus, parietal lobe, cortex, and amygdala. These observations appear to indicate that ZIKV infection may be systemic and persistent regardless of route of inoculation. In addition, we observed changes in key immune cell populations in response to ZIKV infection. Importantly, IVAG ZIKV infection of RMs is associated with increased depletion of CD11C hi myeloid cells, reduced PD-1 expression in NK cells, and elevated frequencies of Ki67(+) CD8(+) central memory cells as compared to sub Q ZIKV-infected RMs. These results need to interpreted with caution due to the small number of animals utilized in this study. Future studies involving large groups of animals that have been inoculated through both routes of transmission are needed to confirm our findings.