Inactivated Wild-Type Zika Virus (strain Uganda MP1751)

Zika virus (ZIKV) causes congenital Zika syndrome, including various alterations in central nervous system development. Although infection of cells of the nervous system has been well documented, little is known about the ability of Zika virus to infect immune cells. Here, researchers investigated whether freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy donors could be infected by Zika virus. They detected Zika virus RNA in PBMCs from all donors by RT-qPCR analysis. Detection of viral antigens by flow cytometry revealed that more than 50% of the donors' PBMCs were infected with Zika virus, with CD3+CD4+ T cells, CD3−CD19+ B cells, and CD3+CD8+ T cells being the most frequently infected subsets, respectively, followed by CD14+ monocytes. Furthermore, there was a wide variation in the infection rate of PBMCs between different donors, both in terms of the number and type of infected cells. These findings raise the hypothesis that PBMCs could act as a reservoir for the virus, which could facilitate viral dissemination to different organs, including immune-privileged sites.

To verify whether the detected viral loads were due to active PBMC infection rather than passive uptake of viral particles, the researchers performed viral titrations in culture supernatants. At 24, 48, and 72 hours post-infection, supernatants from MOCK, inactivated ZIKV, or ZIKV-infected PBMCs were harvested and used to infect Vero cell monolayers. The results showed that viral titrations increased over time, indicating active PBMC infection. The researchers were unable to detect viral particles in the supernatants of MOCK or inactivated ZIKV-infected samples (Figure 1A). This result also suggests that viral particles produced by PBMCs can infect other cells, as the titrations were performed in Vero cells (Figure 1B). Overall, these data clearly indicate that human PBMCs are a target of ZIKV, at least under the experimental conditions applied in this study.

Figure 1. ZIKV viral multiplication in PBMCs. (Messias C V, et al., 2019)