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Titolo:
PHYSICOCHEMICAL DISSOCIATION OF CD4-MEDIATED SYNCYTIUM FORMATION AND SHEDDING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120
Autore:
FU YK; HART TK; JONAK ZL; BUGELSKI PJ;
Indirizzi:
SMITHKLINE BEECHAM PHARMACEUT TOXICOL US,UE0462,709 SWEDELAND RD KINGOF PRUSSIA PA 19406
Titolo Testata:
Journal of virology
fascicolo: 7, volume: 67, anno: 1993,
pagine: 3818 - 3825
SICI:
0022-538X(1993)67:7<3818:PDOCSF>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT SOLUBLE CD4; SEMLIKI FOREST VIRUS; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; MONOCLONAL-ANTIBODIES; AIDS RETROVIRUS; PLASMA-MEMBRANE; VIRAL FUSION; HTLV-III/LAV; CELL-FUSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
Y.K. Fu et al., "PHYSICOCHEMICAL DISSOCIATION OF CD4-MEDIATED SYNCYTIUM FORMATION AND SHEDDING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120", Journal of virology, 67(7), 1993, pp. 3818-3825

Abstract

The mechanism of CD4-mediated fusion via activated human immunodeficiency virus type 1 (HIV-1) gp41 and the biological significance of soluble CD4 (sCD4)-induced shedding of gp120 are poorly understood. The purpose of these investigations was to determine whether shedding of gp120 led to fusion activation or inactivation. BJAB cells (TF228.1.16) stably expressing HIV-1 envelope glycoproteins (the gp120-gp41 complex)were used to examine the effects of pH and temperature on sCD4-induced shedding of gp120 and on cell-to-cell fusion (syncytium formation) with CD4+ SupT1 cells. sCD4-induced shedding of gp120 was maximal at pH4.5 to 5.5 and did not occur at pH 8.5. At physiologic pH, sCD4-induced shedding of gp120 occurred at 22, 37, and 40-degrees-C but neither at 16 nor 4-degrees-C. In contrast, syncytia formed at pH 8.5 (maximally at pH 7.5) but not at pH 4.5 to 5.5. At pH 7.5, syncytia formed at 37 and 40-degrees-C but not at 22, 16, or 4-degrees-C. Preincubation of cocultures of TF228.1.16 and SupT1 cells at 4, 16, or 22-degrees-C before the shift to 37-degrees-C resulted in similar, increased, or decreased syncytium formation, respectively, compared with the control. Furthermore, an activated intermediate of CD4-gp120-gp41 ternary complex may form at 16-degrees-C; this intermediate rapidly executes fusion upon a shift to 37-degrees-C but readily decays upon a shift to the shedding-permissive but fusion-nonpermissive temperature of 22-degrees-C. These physicochemical data indicate that shedding of HIV-1 gp120 is not an integral step in the fusion cascade and that CD4 may inactivatethe fusion complex in a process analogous to sCD4-induced shedding ofgp120.

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Documento generato il 29/11/20 alle ore 00:34:06