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Journal of Virology, January 1999, p. 316-324, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Determinant in Human Immunodeficiency Virus Type 1 for Efficient Replication under Cytokine-Induced CD4+ T-Helper 1 (Th1)- and Th2-Type Conditions

Youichi Suzuki,1 Yoshio Koyanagi,1,* Yuetsu Tanaka,2 Tsutomu Murakami,1 Naoko Misawa,1 Naoyoshi Maeda,1 Tohru Kimura,1 Hisatoshi Shida,3 James A. Hoxie,4 William A. O'Brien,5 and Naoki Yamamoto1

Departments of Microbiology and Molecular Virology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519,1 Department of Biosciences, School of Science, Kitasato University, Sagamihara 228-8555,2 and Institute for Virus Research, Kyoto University, Kyoto 606,3 Japan; Hematology and Oncology Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 191044; and Department of Medicine, University of Texas Medical Branch, Galveston, Texas 775555

Received 30 March 1998/Accepted 21 September 1998

Cytokines are potent stimuli for CD4+-T-cell differentiation. Among them, interleukin-12 (IL-12) and IL-4 induce naive CD4+ T cells to become T-helper 1 (Th1) or Th2 cells, respectively. In this study we found that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains replicated more efficiently in IL-12-induced Th1-type cultures derived from normal CD4+ T cells than did T-cell-line-tropic (T-tropic) strains. In contrast, T-tropic strains preferentially infected IL-4-induced Th2-type cultures derived from the same donor CD4+ T cells. Additional studies using chimeric viruses demonstrated that the V3 region of HIV-1 gp120 was the principal determinant for efficiency of replication. Cell fusion analysis showed that cells expressing envelope protein from a T-tropic strain effectively fused with IL-4-induced Th2-type culture cells. Flow cytometric analysis showed that the level of CCR5 expression was higher on IL-12-induced Th1-type culture cells, whereas CXCR4 was highly expressed on IL-4-induced Th2-type culture cells, although a low level of CXCR4 expression was observed on IL-12-induced Th1-type culture cells. These results indicate that HIV-1 isolates exhibit differences in the ability to infect CD4+-T-cell subsets such as Th1 or Th2 cells and that this difference may partly correlate with the expression of particular chemokine receptors on these cells. The findings suggest that immunological conditions are one of the factors responsible for inducing selection of HIV-1 strains.

* Corresponding author. Mailing address: Department of Microbiology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81-3-5803-5181. Fax: 81-3-5803-0124. E-mail: koyanagi.mmb{at}med.tmd.ac.jp.

Journal of Virology, January 1999, p. 316-324, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.