Stimulation of enveloped virus infection by beta-amyloid fibrils.
Alzheimer's disease is characterized by deposition of beta-amyloid peptide (Abeta) into plaques in the brain, leading to neuronal toxicity and dementia. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system can also cause a dementia, and amyloid deposition in the central nervous system is significantly higher in HIV-1-infected individuals compared with uninfected controls. Here we report that Abeta fibrils stimulated, by 5-20-fold, infection of target cells expressing CD4 and an appropriate coreceptor by multiple HIV-1 isolates but did not permit infection of cells lacking these receptors. Abeta enhanced infection at the stage of virus attachment or entry into the cell. Abeta fibrils also stimulated infection by amphotrophic Moloney leukemia virus, herpes simplex virus, and viruses pseudotyped with the envelope glycoprotein of vesicular stomatitis virus. Other synthetic fibril-forming peptides similarly enhanced viral infection and may be useful in gene delivery applications utilizing retroviral vectors. These data suggest that Abeta deposition may increase the vulnerability of the central nervous system to enveloped viral infection and that amyloidogenic peptides could be useful in enhancing gene transfer by enveloped viral vectors.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Woj M
WM
Wojtowicz
Michael
M
Farzan
John L
JL
Joyal
Kara
K
Carter
Gregory J
GJ
Babcock
David I
DI
Israel
Joseph
J
Sodroski
Tajib
T
Mirzabekov
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D015497:HIV-1 / Q000472:pathogenicity*; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000472:pathogenicity*; D010446:Peptide Fragments / Q000502:physiology*; D018139:Simplexvirus / Q000472:pathogenicity*; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D006583:Hexadimethrine Bromide