Genetic studies of the susceptibility of classical and wild-derived inbred mouse strains to monkeypox virus

Previously, we screened 38 inbred mouse strains for susceptibility to monkeypox virus (MPXV) and focused on wild-derived CAST mice because of their extreme vulnerability. Here, we provide further analysis of inbred mouse strains. NZW/Lac and C58 mice exhibited more weight loss than other classical inbred strains but all survived intranasal challenges with 10(4) to10(6) PFU of MPXV. Mice from three wild derived strains, in addition to CAST, exhibited severe weight loss and died or were euthanized. LD(50) values for CASA, MOLF and PERA were 100, 6800 and >10(5) PFU, respectively. CASA was inbred independently from the same founders as CAST, whereas MOLF and PERA are genetically and geographically distinct. The MPXV susceptibility of the F1 progeny of CAST and either C57BL/6 or BALB/c indicated that resistance is dominant. Back-crossing the F1 progeny of C57BL/6 and CAST to CAST suggested more than one independent resistant locus.