The receptor-binding region of human apolipoprotein E has direct anti-infective activity.
BACKGROUND
The APOE genotype has a uniquely strong influence on the outcome of viral infection. The mechanism is unknown, although one possibility is direct inhibition of viral entry into cells.


METHODS
We have examined the direct anti-infective activity of a peptide analogue of the receptor-binding region of apolipoprotein E (apoE) that is known as "apoE dimer tandem repeat peptide" (apoEdp) and has previously been shown to mimic some of the biological effects of apoE and that recently was shown to bind low-density lipoprotein receptor-related protein.


RESULTS
apoEdp has activity against herpes simplex virus types 1 and 2, human immunodeficiency virus, Pseudomonas aeruginosa, and Staphylococcus aureus; concentrations in the range of 1-20 micromol/L inhibit infection by 50%. These biological actions depend on adoption of an alpha -helical structure, as has been found for other biological effects of apoE peptides. The peptide interferes with the earliest stages of viral infection, preventing viral attachment and exerting a mild virucidal action. In addition, an N-terminal fragment of apoE that also contains this binding domain has antiviral activity.


CONCLUSIONS
These data suggest that human apoE or fragments containing the receptor-binding domain may contribute to innate immunity to viral infection by direct disruption of viral particles and/or inhibition of viral attachment, thus reducing viral entry.
Dobson
Curtis B
CB
Faculty of Life Sciences, The University of Manchester, UK. curtis.dobson@manchester.ac.uk
Sales
Sean D
SD
Hoggard
Patrick
P
Wozniak
Matthew A
MA
Crutcher
Keith A
KA
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D014709:Vero Cells
D000890:Anti-Infective Agents; D001057:Apolipoproteins E; D010446:Peptide Fragments; D018110:Receptors, Lipoprotein