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 chemoki ne receptor 4 (CXCR4) may be intimately involved in the transmission a nd progression of human immunodeficiency virus infection. Changes in c oreceptor 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 CCR 5. This observation had been suggested as an explanation for the sensi tivity of TCLA, but not PI, viruses to neutralization by recombinant g p120 antisera and V3-directed monoclonal antibodies, but recent studie s have shown coreceptor utilization to be independent of neutralizatio n sensitivity. Here we describe a newly isolated TCLA virus that is se nsitive to neutralization but continues to utilize both CXCR4 and CCR5 for infection. This finding further divorces coreceptor specificity f rom neutralization sensitivity and from certain changes in cell tropis m. That the TCLA virus can continue to utilize CCR5 despite the change s that occur upon adaptation and in the apparent absence of CCR5 expre ssion in the FDA/H9 T-cell line suggests that the interaction between envelope protein and coreceptor may be mediated by multiple weak inter actions along a diffuse surface.