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J Gen Virol 75 (1994), 1469-1474; DOI 10.1099/0022-1317-75-6-1469
© 1994 Society for General Microbiology

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Inhibition of infectious human immunodeficiency virus type 1 particle formation by Gag protein-derived peptides

Matthias Niedrig1,{dagger}, Hans R. Gelderblom2, Georg Pauli3, Josefine März4, Heike Bickhard1, Hans Wolf4 and Susanne Modrow4

1 Behringwerke AG, Postfach 1140, D-35001 Marburg
2 Robert Koch-Institut
and3 AIDS-Zentrum des Bundesgesundheitsamtes, Nordufer 20, D-13353 Berlin 35
and4 Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, D-93042 Regensburg, Germany

Sequential overlapping Gag protein-derived oligopeptides of human immunodeficiency virus type 1 (HIV-1) 22 to 24 amino acids long, were synthesized and tested in vitro for antiviral activity. Two synthetic peptides, one derived from the matrix protein p17 (NPGLLETSEGCRQ, amino acids 47 to 59) and one located in the capsid protein p24 (PAATLEEMMTA, amino acids 339 to 349) inhibited the production of infectious virus when added to HIV-1-infected cultures when used in the range of 20 to 200 µg/ml. As shown by thin section electron microscopy, peptide treatment resulted in the release of immature, deformed virus particles suggesting that the two peptides interfered with assembly and maturation. Other Gag protein-derived oligopeptides had little or no influence on virus production. To characterize further the functionally active regions we synthesized peptide derivatives with three consecutive amino acids substituted by alanine; they did not cause inhibition. Therefore the regions responsible for inhibition were located between amino acids 50 to 61 in p17, and 342 to 350 in p24. These observations might lead to the development of a new antiviral strategy affecting the late stage of virus replication.

{dagger} Present address: Robert Koch-Institut, Bundesgesundheitsamt, Nordufer 20, D-13353 Berlin 35, Germany.

Received 21 June 1993; accepted 10 January 1994.


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