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This Week in Science: Dec 27, 2013

A team of Harvard University researchers reports in Science on its examination of insertion mutations into the EGFR exon 20 in non–small cell lung cancer. These mutations, the team notes, are associated with reduced sensitivity to tyrosine kinase inhibitors like gefitinib, erlotinib, and afatinib, which they confirmed in an in vitro study. By looking at the crystal structure of one D770_N771insNPG mutant, the group noted that the binding pocket is unaltered, but that the extra sequence creates a sort of wedge that keeps the protein in an active conformation. These findings, the team adds, may help inform drug development against TKI insensitive tumors.

Also in Science, researchers led by the University of California, San Francisco's Warner Greene report that interferon-gamma–inducible protein 16 acts as a host DNA sensor that triggers an immune response and CD4 T cell death in response to an abortive HIV infection. Using a proteomic approach that coupled DNA affinity chromatography and mass spectrometry, the researchers identified a number of proteins that bind to HIV DNA, including IFI16. A parallel approach using immunoblotting also identified IFI16. "Our findings now identify IFI16 as a critical DNA sensor required for cell death during abortive HIV-1 infection," the researchers note. "Therapies directed against this host pathway might preserve CD4 T cells and reduce chronic inflammation — two signature pathologies in HIV infection."