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Membrane-associated heparan sulfate is not required for rAAV-2 infection of human respiratory epithelia.
Boyle, Michael P; Enke, Raymond A; Reynolds, Jeffrey B; Mogayzel, Peter J; Guggino, William B; Zeitlin, Pamela L.
Afiliação
  • Boyle MP; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore MD 21205, USA. mboyle@jhmi.edu
Virol J ; 3: 29, 2006 Apr 22.
Article em En | MEDLINE | ID: mdl-16630361
ABSTRACT

BACKGROUND:

Adeno-associated virus type 2 (AAV-2) attachment and internalization is thought to be mediated by host cell membrane-associated heparan sulfate proteoglycans (HSPG). Lack of HSPG on the apical membrane of respiratory epithelial cells has been identified as a reason for inefficient rAAV-2 infection in pulmonary applications in-vivo. The aim of this investigation was to determine the necessity of cell membrane HSPG for efficient infection by rAAV-2.

RESULTS:

Rates of transduction with rAAV2-CMV-EGFP3 in several different immortalized airway epithelial cell lines were determined at different multiplicities of infection (MOI) before and after removal of membrane HSPG by heparinase III. Removal of HSPG decreased the efficacy of infection with rAAV2 by only 30-35% at MOI < or = 100 for all of respiratory cell lines tested, and had even less effect at an MOI of 1000. Studies in mutant Chinese Hamster Ovary cell lines known to be completely deficient in surface HSPG also demonstrated only moderate effect of absence of HSPG on rAAV-2 infection efficacy. However, mutant CHO cells lacking all membrane proteoglycans demonstrated dramatic reduction in susceptibility to rAAV-2 infection, suggesting a role of membrane glycosaminoglycans other than HSPG in mediating rAAV-2 infection.

CONCLUSION:

Lack of cell membrane HSPG in pulmonary epithelia and other cell lines results in only moderate decrease in susceptibility to rAAV-2 infection, and this decrease may be less important at high MOIs. Other cell membrane glycosaminoglycans can play a role in permitting attachment and subsequent rAAV-2 internalization. Targeting alternative membrane glycosaminoglycans may aid in improving the efficacy of rAAV-2 for pulmonary applications.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traqueia / Brônquios / Dependovirus / Proteoglicanas de Heparan Sulfato / Proteínas de Membrana Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2006 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traqueia / Brônquios / Dependovirus / Proteoglicanas de Heparan Sulfato / Proteínas de Membrana Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2006 Tipo de documento: Article