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PMID: 9525683 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Alanine substitutions of polar and nonpolar residues in the amino-terminal domain of CCR5 differently impair entry of macrophage- and dualtropic isolates of human immunodeficiency virus type 1.

Journal of virology ·Vol. 72 ·No. 4 ·1998-04-00 ·Pages 3464-8

Rabut GE, Konner JA, Kajumo F, Moore JP, Dragic T

Abstract

Multiple extracellular domains of the CC-chemokine receptor CCR5 are important for its function as a human immunodeficiency virus type 1 (HIV-1) coreceptor. We have recently demonstrated by alanine scanning mutagenesis that the negatively charged residues in the CCR5 amino-terminal domain are essential for gp120 binding and coreceptor function. We have now extended our analysis of this domain to include most polar and nonpolar amino acids. Replacement of alanine with all four tyrosine residues and with serine-17 and cysteine-20 decrease or abolish gp120 binding and CCR5 coreceptor activity. Tyrosine-15 is essential for viral entry irrespective of the test isolate. Substitutions at some of the other positions impair the entry of dualtropic HIV-1 isolates more than that of macrophagetropic ones.

MeSH Terms
Alanine/genetics,metabolism Amino Acid Sequence Binding Sites Cell Line HIV Envelope Protein gp120/metabolism HIV-1/isolation & purification,metabolism HeLa Cells Humans Macrophages/virology Molecular Sequence Data Mutagenesis, Site-Directed Phenylalanine/genetics,metabolism Receptors, CCR5/genetics,metabolism
Chemicals
HIV Envelope Protein gp120 Receptors, CCR5 Phenylalanine Alanine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rabut G E
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
Konner J A
Kajumo F
Moore J P
Dragic T
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.4.3464-3468.1998
Published
1998-04-00
Pages
3464-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109856
Subset
IM
Grants
NIAID NIH HHS · R01 AI041420 · United States
NIAID NIH HHS · R01 AI41420 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.4.3464-3468.1998 PMC Full Text View journal details
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