In this revised proposal Dr. Strauss has responded to the previous review by de-emphasizing studies directed at identifying Togavirus receptors, and elucidating the interactions among the membrane spanning domains of alphavirus membrane glycoproteins. In the opinion of this reviewer this is unfortunate. The nature of the alphavirus receptor remains one of the significant mysteries of virology considering the almost limitless host range of these viruses. Many papers have been published implicating molecules as diverse as the MHC complex and Heparin sulphate. The work of the Strauss group has stood out as most scientifically sound. The molecular interactions among the trans-membrane domains of membrane glycoprotein complexes is poorly understood and the precise interactions forming the icosahedral alphavirus membrane suggest that this ay be one of the few model systems which will yield results. The revision has left the proposal with two specific aims; 1) To study the structure and assembly of alpha and flavi viruses, and 2) To examine the ability of chimeric viruses to serve as vaccines. Progress has been very good. During the preceding period of support Dr. Strauss developed the technique of making chimeric viruses to identify protein domains and sequences critical for virus assembly and function. This has proven a powerful tool which has identified a number of critical interactions in the assembly of the virus and forms a major part of the experimental strategy in this application. Dr. Strauss has made significant observations on the evolutionary relationships among the alphaviruses, the three dimensional structure of the viruses , the identification of virus receptors and the pathogenicity of flavi viruses. This research has resulted in 10 peer reviewed publications and 8 review articles
