Keystone symposium on Molecular Aspects of Viral Immunity: Keystone, Colorado, April 14-20, 2001.

About 200 scientists, students and post doc met at the Keystone Resort for the fourth of the Molecular Aspects of Viral Immunity meetings that was organized by Barry T. Rouse, Thomas J. Braciale, Peter C. Doherty, myself, and Herbert (Skip) W. Virgin, IV. Andrew McMichael (Oxford, UK) gave the Keynote Address on the biology of the human immune response to HIV infection. He described their current very encouraging efforts to develop a vaccine which combines both genetic immunization with a recombinant attenuated vaccinia virus containing s string of different epitopes for both T and B cells. This will go into human testing in Africa after current phase 1 trials in the UK are completed. Innate Immunity. The first scientific session was led off by Christine Biron (Brown), discussing her studies on the regulation of antiviral responses to both murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis Virus (LCMV) by type 1 interferons. She demonstrated that IFN-a enhances the IFN-a response of CD8 T cells, even in the absence of IL-12. David Levy (NYU) described the intricate pathways that result in IFN type 1 synthesis and its effector functions in terms of the receptors, the signal transduction pathways and the regulation of gene expression. He showed compelling data for ISGF3 recruitment of TF2D; using a novel CHIP assay, STAT2 may bind G5N5 to transcribe IFN-inducible genes and distinguished between the pathways used by IFN-a (TAATA independent) and IFN-b (TAATA dependent). Carol Reiss (NYU) reviewed aspects of innate immunity in the central nervous system during viral encephalitis. She focused on unpublished studies, revealing an essential role of the eicosinoids leukotrienes, but an inhibitory role of prostaglandins during host recovery in experimental vesicular stomatitis virus (VSV) encephalitis. The session was closed by Bryan Williams (Cleveland Clinic) who discussed mediators of IFN action. Mice deficient in PKR are lethally infected by VSV; he also showed that PKR may be part of the IKK complex and is required for some signaling through NF-kB by MAP kinases (p38, MKK3/6, JNK, and MKK4). Immunity and Pathogenesis of Chronic Viral Infections. The adult lives of T cells was the topic of Peter Doherty’s (St. Jude’s) presentation. He focused on the Diaspora, that is, the trafficking of T cells from lung to LN to lung in response to influenza infection. Ed Mocarski (Stanford) reviewed the roles of chemokines during human CMV infection. Herpesviruses evade immune responses by producing CXClike chemokines from UL146 and UL147; these proteins mimic IL-8 effects when produced during infection and may play a role in transmission of virus from one infected host to a susceptible new host. Skip Virgin (Washington University) discussed the roles of both host and viral genes which contribute to murine gamma herpesvirus (mHV68) latency, vasculitis, and tumor induction. Viral genes encoding homologues of bcl-2 and cyclin regulate persistence; a regulator of complement activation (vRCA) suppressed host responses as does a chemokine receptor, M3. He also described the mechanisms by which CD8 cells control infection which include perforin and inflammatory cytokine release. The session was concluded by a presentation from Mike Oldstone (Scripps). He discussed his labs long-standing investigations into LCMV infections, focusing on the role of specific viral point mutations which determine receptor se-