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J Virol, June 1998, p. 4633-4642, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 T-Lymphotropic Strains Enter Macrophages via a CD4- and CXCR4-Mediated Pathway: Replication Is Restricted at a Postentry Level

Helena Schmidtmayerova,1,2,* Massimo Alfano,1 Gerard Nuovo,3 and Michael Bukrinsky1

The Picower Institute for Medical Research, Manhasset, New York 110301; Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovakia2; and MGN Medical Research Laboratories, Setauket, New York 117333

Received 26 November 1997/Accepted 3 March 1998

The human immunodeficiency virus type 1 (HIV-1) laboratory strains adapted to T-cell lines, as well as most syncytium-inducing primary isolates, replicate poorly in macrophages, which, beside CD4+ T lymphocytes, are major targets of HIV-1. In the present work, we used a semiquantitative PCR-based technique to study viral entry into cells, kinetics of reverse transcription, and translocation of the viral DNA into the nucleus of macrophages infected with different HIV-1 strains. Our results demonstrate that T-lymphotropic strains efficiently enter macrophages. Entry was inhibited by a monoclonal antibody against CD4 and by stromal cell-derived factor 1alpha , a natural ligand of CXCR4, suggesting that both CD4 and CXCR4 act as receptors on macrophages for HIV-1 T-lymphotropic strains. Analysis of the kinetics of reverse transcription and nuclear import revealed that the most pronounced differences between T-lymphotropic and macrophagetropic strains occurred at the level of nuclear translocation of viral DNA, although a delay in reverse transcription was also observed. These results suggest that postentry steps are critical for restricted replication of T-lymphotropic HIV-1 strains in macrophages.

* Corresponding author. Mailing address: The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030. Phone: (516) 562-9506. Fax: (516) 365-5090. E-mail: hsch{at}picower.edu.

J Virol, June 1998, p. 4633-4642, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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