HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dejucq, N. Search for Related Content PubMed PubMed Citation Articles by Dejucq, N.

(Journal of Leukocyte Biology. 2000;68:331-337.)
© 2000 by Society for Leukocyte Biology

HIV-1 replication in CD4⁺ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function

Wohl Virion Centre, Windeyer Institute of Medical Sciences, London, United Kingdom

Correspondence and current address: Dr. Nathalie Dejucq, GERM-INSERM U435, Campus de Beaulieu, 35 042 Rennes Cedex, France. E-mail: nathalie.dejucq{at}rennes.inserm.fr

We studied the replication of HIV-1 macrophage-tropic CCR5-using strains (R5) in CD4⁺ T cell lines to better understand the switch in co-receptor use of such strains during disease progression and to assess resulting changes in cell tropism. We found that the majority of R5 strains cannot replicate in CD4⁺ T cell lines without adaptation by serial passage. A small minority of primary R5 isolates, however, were able to infect two T cell lines, Molt4 and SupT1. This expanded tropism was due to the use of undetectable levels of CCR5 rather than CXCR4 or alternative receptors. In contrast, HIV-1_SF162 adaptation for replication in the C8166 T cell line was due to the emergence of variant strains that could use CXCR4. Of two variants, one was dual-tropic and one T-tropic, although both could use CCR5 as well as CXCR4. A single mutation in the start codon of the accessory gene vpu accounted for the T-tropic phenotype of the second variant, indicating that a non-functional vpu impairs macrophage tropism. Thus, in vitro and in the absence of an immune response, R5 strains naturally adapt to infect CXCR4⁺ T cell lines. Such adaptation resembles the rare R5 to X4 switch that occurs in vivo. Mutations in accessory genes (e.g., vpu) not required for replication in rapidly dividing cell lines may also occur in vitro, abrogating replication in primary cell types such as macrophages. Such mutations, however, are normally selected against in vivo.

Key Words: macrophage and T cell lines tropism • CXCR4 • CCR5 • Vpu

This article has been cited by other articles:

				L. J. Montaner, C.-F. Perno, and S. Crowe Macrophage infection by HIV-1: focus on viral reservoirs and pathogenesis J. Leukoc. Biol., September 1, 2000; 68(3): 301 - 302. [Full Text] [PDF]