title: Neutralization sensitivity of human immunodeficiency virus type 1 primary isolates to antibodies and CD4-based reagents is independent of coreceptor usage.
abstract: We have investigated whether the identity of the coreceptor (CCR5, CXCR4, or both) used by primary human immunodeficiency virus type 1 (HIV-1) isolates to enter CD4+ cells influences the sensitivity of these isolates to neutralization by monoclonal antibodies and CD4-based agents. Coreceptor usage was not an important determinant of neutralization titer for primary isolates in peripheral blood mononuclear cells. We also studied whether dualtropic primary isolates (able to use both CCR5 and CXCR4) were differentially sensitive to neutralization by the same antibodies when entering U87MG-CD4 cells stably expressing either CCR5 or CXCR4. Again, we found that the coreceptor used by a virus did not greatly affect its neutralization sensitivity. Similar results were obtained for CCR5- or CXCR4-expressing HOS cell lines engineered to express green fluorescent protein as a reporter of HIV-1 entry. Neutralizing antibodies are therefore unlikely to be the major selection pressure which drives the phenotypic evolution (change in coreceptor usage) of HIV-1 that can occur in vivo. In addition, the increase in neutralization sensitivity found when primary isolates adapt to growth in transformed cell lines in vitro has little to do with alterations in coreceptor usage.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: A
authors.initials: A
authors.lastname: Trkola
authors.forename: T
authors.initials: T
authors.lastname: Ketas
authors.forename: V N
authors.initials: VN
authors.lastname: Kewalramani
authors.forename: F
authors.initials: F
authors.lastname: Endorf
authors.forename: J M
authors.initials: JM
authors.lastname: Binley
authors.forename: H
authors.initials: H
authors.lastname: Katinger
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000276:immunology*; D002461:Cell Line, Transformed; D002648:Child; D049452:Green Fluorescent Proteins; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015704:CD4 Antigens; D015483:HIV Antibodies; D008164:Luminescent Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins