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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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