All the animals in the 100 and 1000PFU groups exhibited bioluminescence, whereas only two of the four inoculated with 10PFU were infected. (Beck et al., 2000). Inbred mice can be divided into classical and wild-derived groups. Commonly used laboratory mice belong to the classical group, which are genetically similar to each other and are derived from a small number of progenitors (Goios et al., 2007,Ideraabdullah et al., 2004). In contrast, wild-derived strains are genetically diverse, having been trapped at different locations and times prior to inbreeding. We recently screened a large number of inbred strains of mice for DMAT susceptibility to monkeypox virus (MPXV) DMAT infection (Americo et al., 2010). Of these, 32 were classical inbred strains and 6 were wild-derived. Remarkably, all the classical inbred strains were highly resistant to intranasal MPXV infection, whereas three of the wild-derived strains were susceptible. The most susceptible was CAST/Ei (abbreviated CAST), derived from a wild population of the subspecies Mus musculus castaneous trapped in a grain warehouse in Thailand. The vulnerability of CAST mice to MPXV correlated with a low interferon- response following intranasal infection (Earl et al., 2012). However, CAST mice are not immunodeficient, as vaccination provided complete protection against MPXV (Americo et al., 2010). In addition, the CAST mouse has been reported to be resistant to infection with flaviviruses (Sangster et al., 1993). We are unaware of CAST mouse studies with other infectious agents, although resistance to influenza virus is predicted based on the presence of the interferon regulated Mx gene (Staeheli et al., 1988) and this mouse strain is susceptible to Bacillus anthracus lethal toxin (Moayeri et al., 2004). We were interested in determining whether the susceptibility of CAST mice to MPXV would extend to other members of the orthopoxvirus genus of the chordopoxvirus DMAT subfamily of the Poxviridae (Damon, 2013,Moss, 2013). Vaccinia virus (VACV) and cowpox virus (CPXV) were chosen for this investigation as they are extensively used for pathogenesis, vaccine and anti-viral drug studies in mice (Bray et al., 2000,Smee et al., 2000,Smee et al., 2001). Here we report that that the LD50values for VACV and CPXV are two logs lower in CAST mice than in BALB/c mice, DMAT providing an advantage as a model system. However, there was no significant difference in the susceptibility of CAST and BALB/c mice to herpes simplex virus 1 (HSV-1), an unrelated double-stranded DNA virus. Virus titration and bioluminescence imaging were used to track the spread of phenotypically different strains of VACV and CPXV in the CAST mouse. == Results == == Susceptibility of CAST and BALB/c mice to VACV == We previously reported that CAST mice are highly sensitive to intranasal infection with MPXV and that the LD50is 680 PFU (Americo et al., 2010). In contrast, BALB/c mice exhibited little disease and no mortality when infected with doses of MPXV as high as 107PFU. To determine whether the vulnerability of CAST mice to MPXV extended to other orthopoxviruses, we infected CAST and BALB/c mice Mouse monoclonal to CD34 intranasally with escalating doses of VACV strain Western Reserve (WR). Previous studies had indicated that the LD50for VACV WR in BALB/c mice was between 104and 105PFU. In compliance with NIH guidelines, animals that lost 30% of their weight or appeared moribund were terminated; therefore reported deaths included both natural occurrences and.