title: HIV-1 inactivation by 4-vinylpyridine is enhanced by dissociating Zn(2+) from nucleocapsid protein.
abstract: Selective inactivation of critical cysteine residues in human immunodeficiency virus type one (HIV-1) was observed after treatment with 4-vinylpyridine (4-VP), with and without the membrane-permeable metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN). Chromatographic analysis showed that cysteines contained within nucleocapsid zinc fingers, in the context of whole virus or purified protein, were essentially unreactive, but became reactive when a chelator was included. Virus treated with 4-VP showed only a modest decrease in infectivity; after TPEN addition, nearly complete inactivation of HIV-1 occurred. Similarly, quantitation of viral DNA products from 4-VP-treated virus infections showed no significant effects on reverse transcription, but did show a 14-fold reduction in proviruses; when TPEN was added, a 10(5)-fold decrease in late reverse transcription products was observed and no proviruses were detected. Since 4-VP effectiveness was greatly enhanced by TPEN, this strongly suggests that modification of nucleocapsid zinc fingers is necessary and sufficient for HIV-1 inactivation by sulfhydryl reagents.
authors.affiliation: AIDS Vaccine Program, Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick, Building 535, 4th floor, P.O. Box B, Frederick, Maryland 21702-1201, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Morcock
authors.forename: James A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Sowder
authors.forename: Louis E
authors.initials: LE
authors.lastname: Henderson
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Crise
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gorelick
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D005029:Ethylenediamines / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D038301:Virus Inactivation; D015032:Zinc / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D005029:Ethylenediamines; D019590:Nucleocapsid Proteins; D011725:Pyridines; C029351:4-vinylpyridine; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine