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, Paola Panina Bordignon, Priscilla Biswas, Andrea Brambilla, Chiara Bovolenta, Manuela Cota, Francesco Sinigaglia, Guido Poli

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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- 1(NL)4-3, a chimera in which the env gene had been replaced with that of the R5 HIV-1(NL(AD)8), 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 vital 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 vital transmission and during early-stage disease.

Original languageEnglish
Pages (from-to)7515-7523
Number of pages9
JournalJournal of Virology
Issue number9
Publication statusPublished - 1999


ASJC Scopus subject areas

  • Immunology

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