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Antimicrobial Agents and Chemotherapy, November 2002, p. 3597-3605, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3597-3605.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Tripeptide Interference with Human Immunodeficiency Virus Type 1 Morphogenesis

Stefan Höglund,1* Jin Su,2 Sara Sandin Reneby,1 Ákos Végvári,1 Stellan Hjertén,1 Ida-Maria Sintorn,3 Hillary Foster,1 Yi-Pyng Wu,2 Ingela Nyström,3 and Anders Vahlne2*

Department of Biochemistry, Biomedical Center,1 Centre for Image Analysis, Uppsala University, Uppsala,3 Division of Clinical Virology, Karolinska Institutet, F68 Huddinge University Hospital, Stockholm, Sweden2

Received 22 January 2002/ Returned for modification 23 April 2002/ Accepted 6 August 2002

Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 µM, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolyl-glycine-amide (GPG-NH2), alanyl-leucyl-glycine-amide (ALG-NH2), and arginyl-glutaminyl-glycine-amide (RQG-NH2), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH2 and ALG-NH2. Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.

* Corresponding author. Mailing address for Anders Vahlne: Division of Clinical Virology, Karolinska Institutet, F68 Huddinge University Hospital, SE-141 86 Stockholm, Sweden. Phone: 46-8-5858 1313. Fax: 46-8-5858 7931. E-mail: Anders.Vahlne{at}impi.ki.se. Mailing address for Stefan Högland: Department of Biochemistry, Biomedical Center, Uppsala University, SE-751 23 Uppsala, Sweden. Phone: 46-18-471 4226. Fax: 46-18-552 139. E-mail: Stefan.Hoglund{at}biokem.uu.se.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3597-3605, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3597-3605.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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