Lethal neurotoxicity in mice of the basic domains of HIV and SIV Rev proteins. Study of these regions by circular dichroism.
We have recently reported a basic domain-mediated neurotoxic activity of HIV-1 Tat [1991, J. Virol. 65, 961-965]. Here we have tested the neurotoxicity in vivo of several Rev-related synthetic peptides and found that only those mimicking the basic regions of Rev from HIV-1, HIV-2 and SIV were lethal to mice. In contrast, the homologous domain of HTLV-1 Rex was found to be inactive for lethal activity. Analysis of the tropism of these peptides for phospholipids has demonstrated a direct interaction of the basic domain-containing peptides, except Rex, with acidic--but not neutral--phospholipids. As determined by circular dichroism, a possible correlation between the conformation of the basic regions and the toxicity is discussed.
Mabrouk
K
K
Laboratoire de Biochemie, CNRS URA 1455, Faculté de Médecine Secteur Nord, Marseille, France.
Van Rietschoten
J
J
Vives
E
E
Darbon
H
H
Rochat
H
H
Sabatier
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D015694:Gene Products, rev / Q000235:genetics / Q000633:toxicity*; D016370:Gene Products, rex / Q000235:genetics; D015497:HIV-1 / Q000378:metabolism*; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D009420:Nervous System / Q000187:drug effects*; D009498:Neurotoxins; D010449:Peptide Mapping; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014357:Trypsin; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D016370:Gene Products, rex; D009498:Neurotoxins; D054321:rev Gene Products, Human Immunodeficiency Virus; D014357:Trypsin