Inhibition of human immunodeficiency virus type 1 replication by the K10-K42 peptide of GAP31 is due to induction of rapid but nonspecific precipitation of viral and nonviral proteins

• Published in: AIDS research and human retroviruses Vol. 15; no. 5; p. 429
• Main Authors: Fink, P D, Alexander, I E, Rowe, P B, Smythe, J A
• Format: Journal Article
• Language: English
• Published: United States 20.03.1999
• Subjects: Amino Acid Sequence; Anti-HIV Agents - pharmacology; Cells, Cultured; Chemical Precipitation; Electrophoresis, Polyacrylamide Gel; HIV-1 - drug effects; HIV-1 - physiology; Humans; Molecular Sequence Data; Peptides - chemistry; Peptides - pharmacology; Plant Proteins - chemistry; Ribosome Inactivating Proteins, Type 1; Spectrophotometry; Viral Proteins - chemistry; Virus Replication - drug effects
• ISSN: 0889-2229; 1931-8405
• DOI: 10.1089/088922299311178

The 33-amino acid peptide K10-K42 has previously been described as having potent anti-HIV-1 activity, and antiviral efficacy against hepatitis B and human cytomegalovirus in vitro. Although the exact mechanism of antiviral activity was unknown, it was hypothesised that the K10-K42 peptide inhibited HIV-1 by interfering with one or more of the intracellular processes of reverse transcription, integration, and/or viral gene expression. We performed a series of experiments to identify and characterize the inhibitory mechanism, and to determine whether intracellular expression of the K10-K42 peptide would potentiate its antiviral efficacy in vitro. Surprisingly, our results revealed that the antiviral activity of the K10-K42 peptide could be explained without implicating intracellular inhibition of HIV-1 replication. The activity appeared to be due to an extraordinary capacity of the K10-K42 peptide to precipitate viral and nonviral proteins in vitro. The protein-precipitating capacity of the K10-K42 peptide was sequence specific and a scrambled version of the 33-amino acid peptide did not retain the activity. Although the unusual biochemical properties of the K10-K42 peptide probably negate a number of potential therapeutic applications, they do merit further investigation. Moreover, these findings provide a plausible explanation of the mechanism by which the K10-K42 peptide can inhibit replication of viruses from families as genetically and functionally diverse as Retroviridae, Hepadnaviridae, and Herpesviridae.