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T cell line passage can select for pre-existing neutralization-sensitive variants from the quasispecies of primary human immunodeficiency virus type-1 isolates

By Esther D. Quakkelaar, Tim Beaumont, Ad C. van Nuenen, Floris P. J. van Alphen, Brigitte D. M. Boeser-Nunnink, Angélique B. van 't Wout and Hanneke Schuitemaker


Primary human immunodeficiency type 1 viruses (HIV-1) resist antibody neutralization but become sensitive after passage through T cell lines. We and others previously reported an increased neutralization sensitivity of HIV-1 after prolonged culture on primary peripheral blood mononuclear cells (PBMC). Hence we hypothesized that adaptation to growth in T cell lines is in fact selection of a pre-existing neutralization-sensitive HIV-1 variant from the quasispecies in the PBMC culture. Indeed, increased neutralization sensitivity was associated with largely identical synonymous and non-synonymous mutations between progeny of parallel H9 passages from the same split inoculum from 2 of 3 viruses. H9 T cell line adaptation of molecular cloned HIV-1 was less successful and associated with only a few de novo mutations that varied between parallel H9-adapted progeny from the same split inoculum. We conclude that T cell line adaptation of HIV-1 can indeed select for a pre-existing variant but that this most likely depends on the viral diversity in the inoculu

Year: 2007
DOI identifier: 10.1016/j.virol.2006.09.021
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Provided by: NARCIS
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