MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect.

Abstract

The recent outbreak of monkeypox virus (MPXV) has caused global concern. How the virus evades the interferon (IFN) response is still poorly understood. We analyzed type I/II IFN (IFN-I/II) expression in clinical samples from MPXV-infected patients and measured IFN-I kinetics in MPXV-infected cells. We also evaluated the anti-MPXV activity of IFN-I/II in A549, HeLa and Vero-E6 cell lines. IFN-I/II mRNA expression was detected in skin lesions, anal swabs, nasopharyngeal samples and peripheral blood mononuclear cells (PBMC), with the highest levels in skin lesions (p&#x2009;<&#x2009;0.05). High MPXV DNA levels in clinical samples were associated with increased IFN-I levels. In vitro, MPXV infection induced a peak of IFN-I between 48 and 72&#xa0;h post-infection (p&#x2009;<&#x2009;0.01). Pre-treatment of the A549, HeLa and Vero-E6 cells with high concentrations (&#x2265;&#x2009;100,000 International Unit, IU/ml) of IFN-&#x3b1; and IFN-&#x3c9; did not inhibit or had little effect on MPXV replication, while IFN-&#x3b2; moderately reduced MPXV replication by 2.7-1.5 logat 100,000 IU/ml. In clinical samples there was a trend for elevated levels of IFN-&#x3b3; in association with lower MPXV load and in vitro IFN-&#x3b3; (3,600 IU/ml) strongly reduced viral titers by 3.4-1.6 log. There were no significant differences in expression of select IFN-stimulated genes (ISGs) in MPXV infection in vitro. This study shows that MPXV delays IFN-I induction and inhibits expression of selected ISGs in vitro and is associated with an IFN-I resistance phenotype in vivo. However, MPXV is less resistant to IFN-&#x3b3; in vivo and is sensitive to IFN-&#x3b3; treatment in vitro, suggesting a potential therapeutic role for IFN-&#x3b3;.