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Titolo:
VIRAL MULTIPLICITY OF ATTACHMENT AND ITS IMPLICATIONS FOR HUMAN-IMMUNODEFICIENCY-VIRUS THERAPIES
Autore:
SPOUGE JL;
Indirizzi:
NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8S806 BETHESDA MD 20894
Titolo Testata:
Journal of virology
fascicolo: 3, volume: 68, anno: 1994,
pagine: 1782 - 1789
SICI:
0022-538X(1994)68:3<1782:VMOAAI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT SOLUBLE CD4; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; CD4-BINDING SITE; CELL RECEPTORS; LOWER AFFINITY; HIV-INFECTION; GP120 BINDING; NEUTRALIZATION; TYPE-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
57
Recensione:
Indirizzi per estratti:
Citazione:
J.L. Spouge, "VIRAL MULTIPLICITY OF ATTACHMENT AND ITS IMPLICATIONS FOR HUMAN-IMMUNODEFICIENCY-VIRUS THERAPIES", Journal of virology, 68(3), 1994, pp. 1782-1789

Abstract

The multiplicity of attachment (MOA) of a virion in any particular time interval is the average number of cellular attachment opportunitiesthat must be blocked to keep the virion in suspension. MOA is usuallyproportional to incubation time and cell concentration. Low MOA (likelow multiplicity of infection) is required for reproducible assay of adsorptive blockers, and high MOA by itself can produce spurious synergies between adsorptive blockers, e.g., soluble CD4 (sCD4) and some antibodies. Poliovirus and human immunodeficiency virus (HIV) data show that viral neutralization conforms quantitatively to MOA and kinetic theory over large ranges of incubation times and target cell concentrations. Extrapolating sCD4 data beyond conditions achievable in vitro tothose in vivo predicts that sCD4 concentrations above the strain-specific sCD4-gp120 dissociation constant are required to block lymphoid HIV significantly, in at least semiquantitative agreement with clinicalresults. The extrapolation is applicable to humoral neutralization data as well. MOA analysis also indicates that although completely stopping the attachment of individual virions to cells may still be an effective therapeutic strategy against established HIV infection, merely retarding attachment probably is not. The concept of MOA holds great promise for improving the therapeutic relevance of in vitro data and canbe applied to any infectious agent, to many processes that impair or enhance infection steps, and to many assay end points, not just infection.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 15:04:41