title: Coreceptor utilization by human immunodeficiency virus type 1 is not a primary determinant of neutralization sensitivity.
abstract: We have examined the relationship between coreceptor utilization and sensitivity to neutralization in a primary isolate of human immunodeficiency virus type 1 and its T-cell line-adapted (TCLA) derivative. We determined that adaptation of the primary-isolate (PI) virus 168P results in the loss of the unique capacity of PI viruses to utilize the CCR5 coreceptor and in the acquisition by the TCLA 168C virus of sensitivity to neutralization by V3-directed monoclonal antibodies (MAbs). In experiments wherein infection by 168P is directed via either the CCR5 or the CXCR4 pathway, we demonstrate that the virus, as well as pseudotyped virions bearing a molecularly cloned 168P envelope protein, remains refractory to neutralization by MAbs 257-D, 268-D, and 50.1 regardless of the coreceptor utilized. This study suggests that coreceptor utilization is not a primary determinant of differential neutralization sensitivity in PI and TCLA viruses.
authors.affiliation: Montana Biotechnology Center, The University of Montana, Missoula 59812, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: LaCasse
authors.forename: K E
authors.initials: KE
authors.lastname: Follis
authors.forename: T
authors.initials: T
authors.lastname: Moudgil
authors.forename: M
authors.initials: M
authors.lastname: Trahey
authors.forename: J M
authors.initials: JM
authors.lastname: Binley
authors.forename: V
authors.initials: V
authors.lastname: Planelles
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: J H
authors.initials: JH
authors.lastname: Nunberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral; D015752:Genes, env; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4