contribution of intrinsic reactivity of the hiv-1 envelope glycoproteins to cd4-independent infection and global inhibitor sensitivity贡献的内在反应cd4-independent感染hiv - 1包膜糖蛋白和全球抑制剂的敏感性.pdf

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity 1 1 1 1 1 2 Hillel Haim , Bettina Strack , Aemro Kassa , Navid Madani , Liping Wang , Joel R. Courter , Amy 1 1 1 3 2 Princiotto , Kathleen McGee , Beatriz Pacheco , Michael S. Seaman , Amos B. Smith III , Joseph Sodroski1,4* 1 Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America, 4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, Unites States of America Abstract Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated