PMID- 1326649 OWN - NLM STAT- MEDLINE DCOM- 19921019 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 66 IP - 10 DP - 1992 Oct TI - Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins. PG - 5879-89 AB - Twelve synthetic peptides containing hydrophilic amino acid sequences of human T-cell lymphotropic virus type I (HTLV-I) envelope glycoprotein were coupled to tetanus toxoid and used to raise epitope-specific antisera in goats and rabbits. Low neutralizing antibody titers (1:10 to 1:20) raised in rabbits to peptides SP-2 (envelope amino acids [aa] 86 to 107), SP-3 (aa 176 to 189), and SP-4A (aa 190 to 209) as well as to combined peptide SP-3/4A (aa 176 to 209) were detected in the vesicular stomatitis virus-HTLV-I pseudotype assay. Higher-titered neutralizing antibody responses to HTLV-I (1:10 to 1:640) were detected with pseudotype and syncytium inhibition assays in four goats immunized with a combined inoculum containing peptides SP-2, SP-3, and SP-4A linked to tetanus toxoid. These neutralizing anti-HTLV-I antibodies were type specific in that they did not inhibit HTLV-II syncytium formation. Neutralizing antibodies in sera from three goats could be absorbed with peptide SP-2 (aa 86 to 107) as well as truncated peptides containing envelope aa 90 to 98, but not with equimolar amounts of peptides lacking envelope aa 90 to 98. To map critical amino acids that contributed to HTLV-I neutralization within aa 88 to 98, peptides in which each amino acid was sequentially replaced by alanine were synthesized. The resulting 11 synthetic peptides with single alanine substitutions were then used to absorb three neutralizing goat antipeptide antisera. Both asparagines at positions 93 and 95 were required for adsorption of neutralizing anti-HTLV-I antibodies from all three sera. Peptide DP-90, containing the homologous region of HTLV-II envelope glycoprotein (aa 82 to 97), elicited antipeptide neutralizing antibodies to HTLV-II in goats that were type specific. In further adsorption experiments, it was determined that amino acid differences between homologous HTLV-I and HTLV-II envelope sequences at HTLV-I aa 95 (N to Q) and 97 (G to L) determined the type specificity of these neutralizing sites. Thus, the amino-terminal regions of HTLV-I and -II gp46 contain homologous, linear, neutralizing determinants that are type specific. FAU - Palker, T J AU - Palker TJ AD - Department of Medicine, Duke University Medical Center, Durham, North Carolina. FAU - Riggs, E R AU - Riggs ER FAU - Spragion, D E AU - Spragion DE FAU - Muir, A J AU - Muir AJ FAU - Scearce, R M AU - Scearce RM FAU - Randall, R R AU - Randall RR FAU - McAdams, M W AU - McAdams MW FAU - McKnight, A AU - McKnight A FAU - Clapham, P R AU - Clapham PR FAU - Weiss, R A AU - Weiss RA AU - et al. LA - eng GR - 1P30-AI28662/AI/NIAID NIH HHS/United States GR - CA-440660/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Gene Products, env) RN - 0 (HTLV-I Antibodies) RN - 0 (HTLV-II Antibodies) RN - 0 (Immune Sera) RN - 0 (Peptides) RN - 0 (Retroviridae Proteins, Oncogenic) RN - 0 (env Gene Products, Human Immunodeficiency Virus) RN - 0 (gp46 protein, Human T-cell leukemia virus type I) RN - 0 (gp46 protein, Human immunodeficiency virus 2) SB - IM MH - Amino Acid Sequence MH - Animals MH - Blotting, Western MH - Gene Products, env/genetics/*immunology MH - Goats MH - HTLV-I Antibodies/immunology MH - HTLV-II Antibodies/immunology MH - Immune Sera MH - Immunohistochemistry MH - Molecular Sequence Data MH - Mutation MH - Neutralization Tests MH - Peptides/*genetics MH - Rabbits MH - Radioimmunoassay MH - Retroviridae Proteins, Oncogenic/genetics/*immunology MH - Vesicular stomatitis Indiana virus/metabolism MH - env Gene Products, Human Immunodeficiency Virus PMC - PMC241464 EDAT- 1992/10/01 00:00 MHDA- 1992/10/01 00:01 PMCR- 1992/10/01 CRDT- 1992/10/01 00:00 PHST- 1992/10/01 00:00 [pubmed] PHST- 1992/10/01 00:01 [medline] PHST- 1992/10/01 00:00 [entrez] PHST- 1992/10/01 00:00 [pmc-release] AID - 10.1128/JVI.66.10.5879-5889.1992 [doi] PST - ppublish SO - J Virol. 1992 Oct;66(10):5879-89. doi: 10.1128/JVI.66.10.5879-5889.1992.