Monkeypox Virus Subverts the Inflammatory Response of Macrophages at the Maternal-Fetal Interface.

Abstract

Monkeypox is a viral zoonosis caused by the monkeypox virus (MPXV). Although the virus was identified decades ago, human immunity to MPXV infection has not been widely characterized. During MPXV infection, macrophages are recruited at the site of infection and are thought to contribute to the spread of the virus. Cases of MPXV vertical transmission were reported in infected pregnant women to the developing fetuses in utero resulting to high viral burden in placenta tissue and abortion. We aim to understand the impact of MPXV infection at the foeto-maternal interface by focusing on macrophages functions. Using full-term placental explant model, macrophages were recruited at site of infection. Isolated naive macrophages are permissive to MPXV infection and secrete high levels of pro-inflammatory cytokines associated with a strong M1 polarization profile. Analysis of antiviral gene expression reveals upregulation of IFNA and IFN-associated genes suggesting that MPXV induces the expression of some component of antiviral response from macrophages that are unable to clear the virus. Our study shows that macrophages are permissive to MPXV that subverts inflammatory and antiviral machinery without virus clearance. Such findings contribute to better knowledge of MPXV vertical transmission pathogenesis.