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PMID: 1326649 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins.

Journal of virology ·Vol. 66 ·No. 10 ·1992-10-00 ·Pages 5879-89

Palker TJ, Riggs ER, Spragion DE, Muir AJ, Scearce RM, Randall RR, McAdams MW, McKnight A, Clapham PR, Weiss RA

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Blotting, Western Gene Products, env/genetics,immunology Goats HTLV-I Antibodies/immunology HTLV-II Antibodies/immunology Immune Sera Immunohistochemistry Molecular Sequence Data Mutation Neutralization Tests Peptides/genetics Rabbits Radioimmunoassay Retroviridae Proteins, Oncogenic/genetics,immunology Vesicular stomatitis Indiana virus/metabolism env Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, env HTLV-I Antibodies HTLV-II Antibodies Immune Sera Peptides Retroviridae Proteins, Oncogenic env Gene Products, Human Immunodeficiency Virus gp46 protein, Human T-cell leukemia virus type I gp46 protein, Human immunodeficiency virus 2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Palker T J
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Riggs E R
Spragion D E
Muir A J
Scearce R M
Randall R R
McAdams M W
McKnight A
Clapham P R
Weiss R A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.10.5879-5889.1992
Published
1992-10-00
Pages
5879-89
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC241464
Subset
IM
Grants
NIAID NIH HHS · 1P30-AI28662 · United States
NCI NIH HHS · CA-440660 · United States
External Links
PubMed source DOI: 10.1128/JVI.66.10.5879-5889.1992 PMC Full Text View journal details
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