Isolation and characterization of adociavirin, a novel HIV-inhibitory protein from the sponge Adocia sp.
Aqueous extracts of the New Zealand sponge Adocia sp. (Haplosclerida) displayed potent anticytopathic activity in CEM-SS cells infected with HIV-1. Protein fractions of the extract bound both to the viral coat protein gp120 and to the cellular receptor CD4, but not to other tested proteins. The purified active protein, named adociavirin, was characterized by isoelectric focusing, amino acid analysis, MALDI-TOF mass spectrometry and N-terminal sequencing. Adociavirin, a disulfide-linked homodimer with a native molecular weight of 37 kDa, was active against diverse strains and isolates of HIV-1, as well as HIV-2, with EC50 values ranging from 0.4 nM to > 400 nM. The anti-HIV potency of adociavirin appears dependent on host cell type, with macrophage cultures being the most sensitive and peripheral blood lymphocytes the most resistant.
Laboratory of Drug Discovery Research and Development, Development Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick Cancer Research and Development Center, MD 21702-1201, USA.
B R
BR
O'Keefe
T
T
Erim
J A
JA
Beutler
J H
JH
Cardellina
R J
RJ
Gulakowski
B L
BL
Krepps
J B
JB
McMahon
R C
RC
Sowder
D G
DG
Johnson
R W
RW
Buckheit
S
S
Halliday
M R
MR
Boyd
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D008969:Molecular Sequence Data; D011161:Porifera / Q000737:chemistry*; D011506:Proteins / Q000302:isolation & purification* / Q000378:metabolism / Q000502:physiology
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011506:Proteins; C113471:adociavirin protein, Adocia