AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 9, Number 5, 1993 Mary Ann Liebert, Inc., Publishers An Epitope on the Surface Envelope Glycoprotein (gpl30) of Simian Immunodeficiency Virus (SIVmac) Involved in Viral Neutralization and Cell Activation JOSÉ V. TORRES,* ARTHUR MALLEY,t BABAK BANAPOUR^ DAVID E. ANDERSON,* MICHAEL K. AXTHELM.t MURRAY B. GARDNER, and ELI BENIAMINI* ABSTRACT SIVmac infection of macaques is an important animal model for HIV infection and AIDS; this model is being utilized for development of antiviral therapies and vaccines. In the present article, we sought to identify neutralization epitopes of SIVmac envelope surface glycoprotein (gpl30). Algorithms were used to predict antigenicity of specific regions. Four regions from the primary amino acid sequence of the viral surface glycoprotein were selected. A synthetic peptide representing one of these regions (414-434) induced virus- neutralizing antibodies in mice; in addition, this peptide induced cell-proliferative responses in macaques. To address the in vivo relevance of these observations, we demonstrated that experimentally infected macaques produce antibodies to the neutralization epitope. In addition, rhesus macaques protected against infection by an inactivated SIV vaccine develop antibodies that bind to peptide 414-434. These observations demonstrate that the region that includes the sequence 414-434 in the fourth variable domain ( V 41 of SIVmac gp 130 contains both a linear neutralization epitope and a cell epitope. INTRODUCTION A group of primate lentiviruses, designated simian immuno¬ deficiency viruses (SIV), are genetically related to HIV. Several SIV isolates from African monkeys induce an AIDS-like immunodeficiency syndrome in experimentally infected Asian macaques (reviewed in Refs. 1-3). In addition, SIV and HIV utilize the CD4 molecule as a receptor and infect CD4+ cells4 and macrophages.5'6 Similarities between HIV infection of humans and SIVmac infection of macaques make this system an important animal model for studying the significance of host immune responses in controlling HIV infection.2'7 The outcome of SIV infection in experimentally inoculated animals appears to depend on the host immune response. SIVmac-infected macaques, which respond with high titers of antibodies and cell-proliferative responses, survive for a year or longer.8 In contrast, monkeys that do not develop a significant titer to SIVmac usually die within the first 6 months after infection. Thus, host immune responses appear to delay disease progression. The role of host immune responses has also been investigated in macaques immunized with various vaccine prep¬ arations. Protection against low-dose intravenous infection was achieved by immunizing macaques with inactivated whole SIV vaccines.7 In some studies, vaccine protection correlated better with antibodies directed to cellular antigens present on the surface of human cells (xenogeneic antigens) used to grow the virus than with virus-neutralizing antibodies.910 Nevertheless, these findings do not rule out the possibility that protection against infection by host immune responses is directed to viral protein(s). Vaccine protocols with virus grown in rhesus cells, together with immunological characterization of viral proteins at the epitope level and the use of synthetic immunogens, should help identify the target(s) of the protective immune response. A region of the SIVmac envelope glycoprotein (gpl30) to Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616. tOregon Primate Research Center, Beaverton, OR 97006. tDepartment of Medical Pathology, School of Medicine, University of California, Davis, CA 95616. 423