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.
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.
Fink
P D
PD
The Children's Medical Research Institute, Wentworthville, New South Wales, Australia.
Alexander
I E
IE
Rowe
P B
PB
Smythe
J A
JA
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D011232:Chemical Precipitation; D004591:Electrophoresis, Polyacrylamide Gel; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry*; D054789:Ribosome Inactivating Proteins, Type 1; D013053:Spectrophotometry; D014764:Viral Proteins / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; C071380:GAP31 protein, Gelonium multiflorum; D010455:Peptides; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D014764:Viral Proteins