title: Analysis of the MCMV resistome by ENU mutagenesis.
abstract: The mouse cytomegalovirus (MCMV) resistome is the set of host genes with nonredundant functions in resistance to MCMV infection. By screening 3,500 G(3) germline mutant mice ( approximately 1,750 gamete equivalents), we have identified eight transmissible mutations that create MCMV susceptibility in C57BL/6 mice. Among these, a mutation called Domino was noted to cause macrophage susceptibility to vesicular stomatitis virus (VSV) in vitro. This accessory phenotype was not corrected by type I interferon (IFN), which suggested a defect of the type I IFN pathway. Domino corresponds to a point mutation that alters the DNA binding domain of STAT1, leading to a defect of STAT1 activation. Identification of the Domino mutation demonstrates that an in vivo MCMV susceptibility screen is feasible and illustrates how it can provide insight into the resistome. Moreover, some mutations are far more deleterious than Domino in MCMV-infected mice, consistent with the interpretation that certain protein(s) unrelated to IFN production or signaling are more important than IFNs with regard to their net antiviral effects.
authors: Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA. bruce@scripps.edu
authors: Karine
authors: K
authors: Crozat
authors: Philippe
authors: P
authors: Georgel
authors: Sophie
authors: S
authors: Rutschmann
authors: Navjiwan
authors: N
authors: Mann
authors: Xin
authors: X
authors: Du
authors: Kasper
authors: K
authors: Hoebe
authors: Bruce
authors: B
authors: Beutler