Abstract
BackgroundMumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeV in vitro.MethodsAnti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot.ResultsThe current work demonstrates that retinoids inhibit MuV in vitro due to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours.ConclusionsThese results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection.
Highlights
Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV)
Mumps virus can be inhibited in vitro U937 cells are neoplastic and histiocytic progenitors of monocytes that have been extensively used in immunological studies [49] including investigation of interferon pathways during MuV infection [50,51,52]
In these cells, increasing doses of retinol resulted in a significant inhibition of MuV replication as quantified by Tissue culture infectious dose50 (TCID50) (Figure 1A)
Summary
Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Richardson, Dalhousie University, Halifax, NS), Vero cells (ATCC, #CCL-81) were maintained as described in [47]. The Jones MuV strain (ATCC, #VR-365) is a tissue culture-adapted virus that was, according to the supplier’s web-site, extensively passaged in chicken embryos and Vero cells prior to purchase. Our MuV stock was initially plaque purified and grown by infecting Vero cells with a maximum passage of three times from the original purchase (ATCC, #CCL-81) at a multiplicity of infection (MOI) of 0.001 at 33°C in a Cell-Stack 10 (Corning, Corning, NY). The Chicago-1 MeV strain is a tissue culture-adapted genotype D3 virus MeV stock was grown as described in [47]
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