Comparison of SIVmac239(352-382) and SIVsmmPBj41(360-390) enterotoxic synthetic peptides.
To characterize the active domain of the simian immunodeficiency virus (SIV) surface unit (SU) enterotoxin, peptides corresponding to the V3 loop of SIVmac239 (SIVmac) and SIVsmmPBj41 (SIVpbj) were synthesized and examined for enterotoxic activity, alpha-helical structure, and interaction(s) with model membranes. SIVmac and SIVpbj induced a dose-dependent diarrhea in 6-8-day-old mouse pups similar to full-length SU. The peptides mobilized [Ca(2+)](i) in HT-29 cells with distinct oscillations and elevated inositol triphosphate levels. Circular dichroism analyses showed the peptides were predominantly random coil in buffer, but increased in alpha-helical content when placed in a hydrophobic environment or with cholesterol-containing membrane vesicles that are rich in anionic phospholipids. None of the peptides underwent significant secondary structural changes in the presence of neutral vesicles indicating ionic interactions were important. These data show that the SIV SU enterotoxic domain localizes in part to the V3 loop region and interacts with anionic membrane domains on the host cell surface.
Swaggerty
C L
CL
Department of Pathobiology, College of Veterinary Medicine, Texas A&M University, TAMU 4467, College Station, TX 77843-4467, USA.
Huang
H
H
Lim
W S
WS
Schroeder
F
F
Ball
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000821:virology; D003967:Diarrhea / Q000503:physiopathology / Q000821:virology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000737:chemistry / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000472:pathogenicity*
D004768:Enterotoxins; D010455:Peptides; D002118:Calcium