Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity
Open Access
- 18 March 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Immunology
- Vol. 11 (1), 13
- https://doi.org/10.1186/1471-2172-11-13
Abstract
Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B-derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides.Keywords
This publication has 24 references indexed in Scilit:
- Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro , and the APOE ε4/ε4 genotype accelerates HIV disease progressionProceedings of the National Academy of Sciences of the United States of America, 2008
- The Receptor‐Binding Region of Human Apolipoprotein E Has Direct Anti‐Infective ActivityThe Journal of Infectious Diseases, 2006
- Evaluating Neutralizing Antibodies Against HIV, SIV, and SHIV in Luciferase Reporter Gene AssaysCurrent Protocols in Immunology, 2004
- Apolipoprotein E polymorphisms and risk of malariaJournal of Medical Genetics, 2004
- Do infectious agents play a role in dementia?Trends in Microbiology, 2003
- Apolipoprotein E-ϵ4 protects against severe liver disease caused by hepatitis C virusHepatology, 2002
- Clusterin, a Binding Protein with a Molten Globule-like RegionBiochemistry, 2001
- Herpes simplex virus type 1 and Alzheimer’s diseaseNeurobiology of Aging, 1999
- Conformational studies of an amphipathic peptide corresponding to human apolipoprotein A‐II residues 18‐30 with a C‐terminal lipid binding motif EWLNSInternational Journal of Peptide and Protein Research, 1996
- Binding of a high reactive heparin to human apolipoprotein E: Identification of two heparin-binding domainsBiochemical and Biophysical Research Communications, 1986