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Journal of Virology, March 2003, p. 3832-3837, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3832-3837.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effect of Amino Acid Substitution of the V3 and Bridging Sheet Residues in Human Immunodeficiency Virus Type 1 Subtype C gp120 on CCR5 Utilization

Pirada Suphaphiphat,1 Arunee Thitithanyanont,2 Saowakon Paca-Uccaralertkun,2 Max Essex,1 and Tun-Hou Lee1*

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115,1 Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand2

Received 8 October 2002/ Accepted 4 December 2002

The V3 loop and the bridging sheet domain of human immunodeficiency virus type 1 (HIV-1) subtype B envelope glycoprotein gp120 have been implicated in CCR5 coreceptor utilization. In this study, mutant envelope glycoproteins of a subtype C isolate containing substitutions in the V3 or C4 region were generated to determine which are required for efficient CCR5-dependent cell fusion and viral entry. We found that the V3 crown and C4 residues are relatively dispensable for cell-cell fusion, although some residues may be involved in the regulation of early postentry steps in viral replication. In contrast, seven highly conserved residues located in the V3 stem are critical for CCR5 utilization, which can explain the apparent paradox that the functional convergence in CCR5 usage by genetically divergent HIV-1 strains involves a variable region. The finding that C4 residues do not have a critical role may appear to contradict the current model that bridging sheet residues are involved in the gp120-CCR5 interaction. However, a plausible interpretation is that these C4 residues may have a distinct role in the binding and fusion steps of the gp120-CCR5 interaction.


* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-1332. Fax: (617) 739-8348. E-mail: tunhoule{at}hsph.harvard.edu.


Journal of Virology, March 2003, p. 3832-3837, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3832-3837.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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