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Titolo:
Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein
Autore:
Le Pogam, S; Yuan, TTT; Sahu, GK; Chatterjee, S; Shih, CH;
Indirizzi:
Univ Texas, Med Branch, Dept Pathol, Ctr Trop Dis, Galveston, TX 77555 USAUniv Texas Galveston TX USA 77555 , Ctr Trop Dis, Galveston, TX 77555 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 19, volume: 74, anno: 2000,
pagine: 9099 - 9105
SICI:
0022-538X(200010)74:19<9099:LSOHHB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPATOMA-CELL LINE; CORE ANTIGEN; HBV-DNA; HEPATOCELLULAR-CARCINOMA; TRANSIENT EXPRESSION; FULMINANT-HEPATITIS; IMMATURE SECRETION; HIGHLY FREQUENT; INFECTION; GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Shih, CH Univ Texas, Med Branch, Dept Pathol, Ctr Trop Dis, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 p Dis, Galveston, TX 77555 USA
Citazione:
S. Le Pogam et al., "Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein", J VIROLOGY, 74(19), 2000, pp. 9099-9105

Abstract

The functional significance of naturally occurring variants of human hepatitis B virus (HEV) remains largely unkown. Previously, we reported an immature secretion phenotype caused by a highly frequent mutation at amino acid 97 of the HBV core (capsid) protein (HBcAg), This phenotype is characterized by a nonselective and excessive secretion of virions containing an immature genome of single-stranded viral DNA, To extend our study of virion secretion to other naturally occurring variants, we have characterized mutationsat HBcAg codons 5, 38, and 60 via site-directed mutagenesis. Although the phenotype of the mutation at codon 38 is nearly identical to that for the wild-type virus, our study reveals that a single mutation at codon 5 or 60 exhibits a new extracellular phenotype,vith significantly reduced virion secretion get maintains normal intracellular viral DNA replication A complementation study indicates that the mutant core protein alone is sufficient forthe "low-secretion" phenotype. Furthermore, the low-secretion phenotype ofthe codon 5 mutant appears to be induced by the loss of a parental prolineresidue, rather than by the gain of a new amino acid. Our study underscores the core protein as another crucial determinant in virion secretion, in addition to the known envelope proteins. Our present results suggest that a very precise structure of both alpha-helical and nonhelical loop regions ofthe entire HBcAg molecule is important for virion secretion. The low-secretion variants may contribute to the phenomenon of gradually decreasing viremia in chronic carriers during the late phase of persistent infection.

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Documento generato il 05/12/20 alle ore 13:59:36