v3 loop truncations in hiv-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodiesv3环截断在hiv - 1信封传授抵抗coreceptor抑制剂和增强对中和抗体.pdfVIP

V3 Loop Truncations in HIV-1 Envelope Impart Resistance to Coreceptor Inhibitors and Enhanced Sensitivity to Neutralizing Antibodies 1 1 2 1 2 1 Meg M. Laakso , Fang-Hua Lee , Beth Haggarty , Caroline Agrawal , Katrina M. Nolan , Mark Biscone , Josephine Romano2 2 2 3,4 3,4 2 , Andrea P. O. Jordan , George J. Leslie , Eric G. Meissner , Lishan Su , James A. Hoxie , 1* Robert W. Doms 1 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 3 Department of Microbiology and Immunology, The University of North Carolina, Chapel Hill, North Carolina, United States of America, 4 The Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina, United States of America The V1/V2 region and the V3 loop of the human immunodeficiency virus type I (HIV-1) envelope (Env) protein are targets for neutralizing antibodies and also play an important functional role, with the V3 loop largely determining whether a virus uses CCR5 (R5), CXCR4 (X4), or either coreceptor (R5X4) to infect cells. While the sequence of V3 is variable, its length is highly conserved. Structural studies indicate that V3 length may be important for interactions with the extracellular loops of the coreceptor. Consistent with this view, genetic truncation of the V3 loop is typically associated with loss of Env function. We removed approximately one-half of the V3 loop from three different HIV-1 strains, and found that only the Env protein f