Antiviral Effect of Manganese against Foot-and-Mouth Disease Virus Both in PK15 Cells and Mice

Abstract

Foot-and-mouth disease (FMD) is an acute contagious disease of cloven-hoofed animals such as cattle, pigs, and sheep. Current emergency FMD vaccines are of limited use for early protection because their protective effect starts 7 days after vaccination. Therefore, antiviral drugs or additives are used to rapidly stop the spread of the virus during FMD outbreaks. Manganese (Mn2+) was recently found to be an important substance necessary for the host to protect against DNA viruses. However, its antiviral effect against RNA viruses remains unknown. In this study, we found that Mn2+ has antiviral effects on the FMD virus (FMDV) both in PK15 cells and mice. The inhibitory effect of Mn2+ on FMDV involves NF-κB activation and up-regulation of interferon-stimulated genes. Animal experiments showed that Mn2+ can be highly effective in protecting C57BL/6N mice from being infected with FMDV. Overall, we suggest Mn2+ as an effective antiviral additive for controlling FMDV infection.

A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells

“…A recent study demonstrated that the combined regimen of Mn 2+ and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with tumors [11]. Our recent study showed that Mn 2+ can be highly effective in protecting C57BL/6N mice from being infected with FMDV [9], indicating that Mn 2+ is an effective antiviral additive for controlling viral infection in vivo. Therefore, it would be beneficial to carry out further study to explore their therapeutic potential against viral infection.…”

“…There's a study that demonstrated that Mn 2+ can promote STING activity by enhancing the binding affinity of 2 , 3 -cyclic guanosine monophosphateadenosine monophosphate (cGAMP) to STING and then induce the potent immunity against DNA viruses [8]. In addition, it was reported that Mn 2+ can also induce the immune response against the infection with RNA viruses, including Newcastle disease virus (NDV), foot-and-mouth disease virus (FMDV) and Sendai virus (SeV) [8][9][10]. A recent study discovered that Mn 2+ is also essential in the innate immune sensing of tumors via cGAS-STING [11].…”

Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle

“…The currently approved chemically inactivated whole virus FMD vaccine ( Doel, 2003 ), and an adenoviral vectored subunit FMD vaccine (Ad5-FMDV) approved for emergency use in the United States ( Grubman et al, 2010 ; Moraes et al, 2011 ), take at least 7 days to confer protection to vaccinated animals, during which time they are still susceptible to infection. There is a significant focus on developing biotherapeutics ( Medina et al, 2020b ; Kim et al, 2022 ) or antiviral agents ( Li et al, 2019 ; Mei-Jiao et al, 2019 ; Naeem et al, 2021 ; Zhang et al, 2023 ) to prevent the occurrence of FMDV infections during the vulnerable period prior to vaccine-induced humoral immunity, thereby closing this window of susceptibility.…”