Dynamin is required for recombinant adeno-associated virus type 2 infection

Dongsheng Duan, Qiang Li, Aimee W. Kao, Yongping Yue, Jeffrey E. Pessin, John F. Engelhardt

Research output: Contribution to journalArticle

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Abstract

Recombinant adeno-associated virus (rAAV) vectors for gene therapy of inherited disorders have demonstrated considerable potential for molecular medicine. Recent identification of the viral receptor and coreceptors for AAV type 2 (AAV-2) has begun to explain why certain organs may demonstrate higher efficiencies of gene transfer with this vector. However, the mechanisms by which AAV-2 enters cells remain unknown. In the present report, we have examined whether the endocytic pathways of rAAV-2 are dependent on dynamin, a GTPase protein involved in clathrin-mediated internalization of receptors and their ligands from the plasma membrane. Using a recombinant adenovirus expressing a dominant-inhibitory form of dynamin I (K44A), we have demonstrated that rAAV-2 infection is partially dependent on dynamin function. Overexpression of mutant dynamin I significantly inhibited AAV-2 internalization and gene delivery, but not viral binding. Furthermore, colocalization of rAAV and transferrin in the same endosomal compartment provides additional evidence that clathrin-coated pits are the predominant pathway for endocytosis of AAV-2 in HeLa cells.

Original languageEnglish (US)
Pages (from-to)10371-10376
Number of pages6
JournalJournal of Virology
Volume73
Issue number12
StatePublished - Dec 1999
Externally publishedYes

Fingerprint

Dependovirus
Dynamins
Virus Diseases
Adeno-associated virus 2
Dynamin I
clathrin
Clathrin
gene transfer
infection
Molecular Medicine
receptors
gene therapy
GTP Phosphohydrolases
guanosinetriphosphatase
endocytosis
genetic disorders
Adenoviridae
transferrin
Transferrin
Endocytosis

ASJC Scopus subject areas

  • Immunology

Cite this

Duan, D., Li, Q., Kao, A. W., Yue, Y., Pessin, J. E., & Engelhardt, J. F. (1999). Dynamin is required for recombinant adeno-associated virus type 2 infection. Journal of Virology, 73(12), 10371-10376.

Dynamin is required for recombinant adeno-associated virus type 2 infection. / Duan, Dongsheng; Li, Qiang; Kao, Aimee W.; Yue, Yongping; Pessin, Jeffrey E.; Engelhardt, John F.

In: Journal of Virology, Vol. 73, No. 12, 12.1999, p. 10371-10376.

Research output: Contribution to journalArticle

Duan, D, Li, Q, Kao, AW, Yue, Y, Pessin, JE & Engelhardt, JF 1999, 'Dynamin is required for recombinant adeno-associated virus type 2 infection', Journal of Virology, vol. 73, no. 12, pp. 10371-10376.
Duan D, Li Q, Kao AW, Yue Y, Pessin JE, Engelhardt JF. Dynamin is required for recombinant adeno-associated virus type 2 infection. Journal of Virology. 1999 Dec;73(12):10371-10376.
Duan, Dongsheng ; Li, Qiang ; Kao, Aimee W. ; Yue, Yongping ; Pessin, Jeffrey E. ; Engelhardt, John F. / Dynamin is required for recombinant adeno-associated virus type 2 infection. In: Journal of Virology. 1999 ; Vol. 73, No. 12. pp. 10371-10376.
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