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Mice lacking the perforin gene were generated by using targeted gene disruption in embryonal stem cells. When infected with lymphocytic choriomeningitis virus (LCMV), perforin-less (-/-) mice showed clear signs of having mounted an immune response based on activation of CD8 T cells but were unable to clear the LCMV infection. This failure to eliminate virus(More)
Investigating genomic structural variants at basepair resolution is crucial for understanding their formation mechanisms. We identify and analyse 8,943 deletion breakpoints in 1,092 samples from the 1000 Genomes Project. We find breakpoints have more nearby SNPs and indels than the genomic average, likely a consequence of relaxed selection. By investigating(More)
Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that perforin also plays a role in immune regulation. Perforin-deficient (perf -/-) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral T cells compared to persistently infected +/+ mice. The enhanced expansion(More)
A simple and rapid procedure for determining the genotypes of viruses has been applied to analysis of genome subunit reassortment in heterologous crosses of Batai virus, Bunyamwera virus, and Maguari virus, three members of the Bunyamwera serogroup of bunyaviruses. The procedure for determining genotype made use of specific molecular probes to identify the(More)
Most clinical studies suggest that corticosteroids are contraindicated in the treatment of acute smoke inhalation. However, they are still used in critical situations with the hope that they might reverse the acute pathophysiological responses to smoke inhalation and thus reduce the severity of the illness or make survival possible. These experiments were(More)
Fetal rat pancreases frozen to and stored at -196 C were used for transplantation into streptozotocin-induced diabetic syngeneic adult recipients. Transplantation was carried out either directly after thawing from -196 C, or after a 21-day growth period in a syngeneic, normoglycemic adult carrier. All transplants were placed under the kidney capsule. A(More)
Mice deficient in perforin, a key mediator of lymphocyte-mediated cytolysis, have recently been generated using the gene knockout technique. CTL and NK cells derived from these mice have been shown to be defective in the granule-dependent cytolytic pathway. To investigate whether the granule-formation process has been altered in these perforin-deficient(More)
We have used a perforin-less (PO) mouse to explore alternate CTL-mediated lytic pathways. PO mice are unable to overcome an infection with LCMV in vivo. Nevertheless, splenocytes from infected mice show vigorous, antigen-specific cytotoxicity that requires the presence of the Fas antigen on target cells. The Fas lytic pathway is virtually indistinguishable,(More)