Continued utilization of CCR5 coreceptor by a newly derived T-cell line-adapted isolate of human immunodeficiency virus type 1.
The differential use of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) may be intimately involved in the transmission and progression of human immunodeficiency virus infection. Changes in coreceptor utilization have also been noted upon adaptation of primary isolates (PI) to growth in established T-cell lines. All of the T-cell line-adapted (TCLA) viruses studied to date utilize CXCR4 but not CCR5. This observation had been suggested as an explanation for the sensitivity of TCLA, but not PI, viruses to neutralization by recombinant gp120 antisera and V3-directed monoclonal antibodies, but recent studies have shown coreceptor utilization to be independent of neutralization sensitivity. Here we describe a newly isolated TCLA virus that is sensitive to neutralization but continues to utilize both CXCR4 and CCR5 for infection. This finding further divorces coreceptor specificity from neutralization sensitivity and from certain changes in cell tropism. That the TCLA virus can continue to utilize CCR5 despite the changes that occur upon adaptation and in the apparent absence of CCR5 expression in the FDA/H9 T-cell line suggests that the interaction between envelope protein and coreceptor may be mediated by multiple weak interactions along a diffuse surface.
Montana Biotechnology Center, The University of Montana, Missoula, Montana 59812, USA.
K E
KE
Follis
M
M
Trahey
R A
RA
LaCasse
J H
JH
Nunberg
D000220:Adaptation, Biological; D001483:Base Sequence; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000821:virology*; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5