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Journal of Virology, September 1999, p. 7515-7523, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Envelope-Dependent Restriction of Human Immunodeficiency Virus Type 1 Spreading in CD4+ T Lymphocytes: R5 but Not X4 Viruses Replicate in the Absence of T-Cell Receptor Restimulation

Elisa Vicenzi,1,* Paola Panina Bordignon,2 Priscilla Biswas,1 Andrea Brambilla,1 Chiara Bovolenta,1 Manuela Cota,1 Francesco Sinigaglia,2 and Guido Poli1

AIDS Immunopathogenesis Unit, DIBIT, San Raffaele Scientific Institute,1 and Roche Milano Ricerche,2 20132 Milan, Italy

Received 16 February 1999/Accepted 21 May 1999

The human immunodeficiency virus (HIV) replicates in activated CD4+ T lymphocytes. However, only CD4+ Th2 and Th0, but not Th1, CD4+ T-cell clones have been reported to efficiently support HIV-1 replication. This dichotomous pattern was further investigated in the present study in Th1, Th2, or Th0 cell lines derived from umbilical human cord blood and in T-cell clones obtained from the peripheral blood mononuclear cells (PBMC) of healthy adults. Both primary and laboratory-adapted HIV-1 strains with CCR5 as the exclusive entry coreceptor (R5 viruses) efficiently replicated in Th1, Th2, and Th0 cells. In sharp contrast, CXCR4-dependent (X4) viruses poorly replicated in both polarized and unpolarized CD4+ T cells, including adults' PBMC infected several days after mitogenic stimulation. Unlike the X4 HIV-1NL4-3, a chimera in which the env gene had been replaced with that of the R5 HIV-1NL(AD8), efficiently replicated in both Th1 and Th2 cells. This X4-dependent restriction of HIV replication was not explained by either the absence of functional CXCR4 on the cell surface or by the inefficient viral entry and reverse transcription. T-cell receptor stimulation by anti-CD3 monoclonal antibodies fully rescued X4 HIV-1 replication in both Th1 and Th2 cells, whereas it did not alter the extent and kinetics of R5 HIV-1 spreading. Thus, R5 HIVs show a replicative advantage in comparison to X4 viruses in their ability to efficiently propagate among suboptimally activated T lymphocytes, regardless of their polarized or unpolarized functional profiles. This observation may help to explain the absolute predominance of R5 HIVs over X4 viruses observed after viral transmission and during early-stage disease.


* Corresponding author. Mailing address: P2-P3 Laboratories, DIBIT, Via Olgettina 58, 20132 Milan, Italy. Phone: 39-02-2643-4908. Fax: 39-02-2643-4905. E-mail: vicenzi.elisa{at}hsr.it.


Journal of Virology, September 1999, p. 7515-7523, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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