Structure-function relationships of HIV1 envelope V3 loop in regulation of host cell tropism. NLM AIDSLINE Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

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Structure-function relationships of HIV1 envelope V3 loop in regulation of host cell tropism.

Int Conf AIDS. 1992 Jul 19-24;8(1):Mo20 (abstract no. MoA 0074). Unique Identifier : AIDSLINE ICA8/92400033
Ebenbichler C; Gu R; Henkel T; Westervelt P; Ratner L; Department of Medicine, Washington University School of Medicine,; St. Louis.

Abstract: OBJECTIVE: To identify the determinants within env that regulate host cell tropism, and analyse their structural features and mechanism of action. RESULTS: Chimeric viruses were constructed with sequences from a monocyte-tropic isolate (ADA) or those from brain or spleen tissues of AIDS patients together with sequences from isolates incapable of macrophage infection (NLHX). In each case, the tropism determinant mapped to a 94 amino acid portion of the gp120 envelope protein (tropism domain) that includes the principal neutralization domain (V3 loop). Comparisons of tropism domain sequences of 3 non-macrophage tropic and 8 macrophage-tropic clones demonstrated that residues in (275,283,287) or adjacent to (313) the V3 loop were different between clones with different tropism. Mutation of residue 287 from K (in HX) to E (in ADA) conferred partial activity. Each of the chimeric envelope proteins were expressed in recombinant vaccinia viruses in a monkey kidney cell line and in primary human lymphocytes and macrophages. The envelope proteins capable of conferring macrophage infection showed less cleavage in the V3 loop by a cell surface protease than did those envelope proteins which did not allow macrophage infection. Similar results were obtained in thrombin or tryptase cleavage studies of purified envelope proteins produced in an insect cell system. Antibody reactivity studies demonstrated a different conformation for the V3 loop of the macrophage tropic envelope proteins than the non-permissive envelopes. SUMMARY: A macrophage tropism domain for envelope has been mapped to a 94 amino acid segment including the V3 loop; residue 287 was shown to be partially responsible for this activity. Altered antibody reactivity and limited susceptibility for V3 loop cleavage correlate closely with macrophage tropism. These findings suggest that a host cell protease which cleaves V3 may be responsible for regulating HIV1 infection of macrophages.
Keywords: Acquired Immunodeficiency Syndrome/MICROBIOLOGY Brain/MICROBIOLOGY Genes, env Genes, Synthetic Human HIV Envelope Protein gp120/*CHEMISTRY/GENETICS/PHYSIOLOGY HIV-1/GENETICS/ISOLATION & PURIF/*PHYSIOLOGY Macrophages/MICROBIOLOGY Peptide Fragments/*CHEMISTRY/GENETICS/PHYSIOLOGY Peptide Peptidohydrolases/METABOLISM Spleen/MICROBIOLOGY Structure-Activity Relationship Substrate Specificity ABSTRACTKWDacquiredimmunodeficiencysyndrome/microbiologybrain/microbiologygenes,envgenes,synthetichumanhivenvelopeproteingp120/KWDchemistry/genetics/physiologyhiv-1/genetics/isolation&purif/KWDphysiologymacrophages/microbiologypeptidefragments/KWDchemistry/genetics/physiologypeptidepeptidohydrolases/metabolismspleen/microbiologystructure-activityrelationshipsubstratespecificityabstract
921230
M92C5314

Copyright © 1992 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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