To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1 -/-mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/-mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-i and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/-mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/-mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1-/-mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/-mice, there was no signaling in response to IFN-a or -,B as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-a and -1.

Motivation: Shotgun sequence read data derived from xenograft material contains a mixture of reads arising from the host and reads arising from the graft. Classifying the read mixture to separate the two allows for more precise analysis to be performed.Results: We present a technique, with an associated tool Xenome, which performs fast, accurate and specific classification of xenograft-derived sequence read data. We have evaluated it on RNA-Seq data from human, mouse and human-in-mouse xenograft datasets.Availability: Xenome is available for non-commercial use from http://www.nicta.com.au/bioinformaticsContact: tom.conway@nicta.com.au