Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells

Shuang Huang, Tetsuji Kamata, Yoshikazu Takada, Zaverio M. Ruggeri, Glen R. Nemerow

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

A major impediment to the effective use of adenovirus vectors for gene therapy is a lack of knowledge of how these vectors interact with diverse cell types in vivo. Adenovirus attachment to most human cell types is mediated by the fiber protein, which binds to an as yet unidentified cell receptor. In contrast to this, we report that adenovirus type 2 (Ad2) attachment to hematopoietic cells is facilitated by interaction of the penton base protein with members of the β2 integrin family. Adenovirus particles were capable of binding to human monocytic cells, which lack fiber receptors, and virus binding could be blocked by a soluble penton base or by a function- blocking monoclonal antibody to integrin α(M)β2. To confirm the role of α(M)β2 integrins in Ad2 binding to hematopoietic cells, we analyzed virus attachment and gene delivery to CHO cells expressing recombinant β2 integrins. α(M)β2-expressing CHO cells supported 3- to 5-fold-higher levels of Ad2 binding and 5- to 10-fold-larger amounts of gene delivery than did nontransfected CHO cells, indicating that α(M)β2 facilitates adenovirus attachment to and infection of hematopoietic cells. While β2 integrins promote Ad2 attachment to hematopoietic cells, further studies demonstrated that αv integrins were required for the next step in infection, virus internalization into cell endosomes. These studies reveal a novel pathway of Ad2 infection of hematopoietic cells mediated by distinct integrins which facilitate separate events in virus entry. They also suggest a possible strategy for selective adenovirus-mediated gene delivery to hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)4502-4508
Number of pages7
JournalJournal of Virology
Volume70
Issue number7
StatePublished - Jun 27 1996

Fingerprint

integrins
Adenoviridae
gene transfer
Integrins
Genes
cells
CHO Cells
Virus Attachment
Virus Internalization
viruses
Adenoviridae Infections
Blocking Antibodies
Endosomes
infection
Infection
receptors
endosomes
Genetic Therapy
gene therapy
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Huang, S., Kamata, T., Takada, Y., Ruggeri, Z. M., & Nemerow, G. R. (1996). Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells. Journal of Virology, 70(7), 4502-4508.

Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells. / Huang, Shuang; Kamata, Tetsuji; Takada, Yoshikazu; Ruggeri, Zaverio M.; Nemerow, Glen R.

In: Journal of Virology, Vol. 70, No. 7, 27.06.1996, p. 4502-4508.

Research output: Contribution to journalArticle

Huang, S, Kamata, T, Takada, Y, Ruggeri, ZM & Nemerow, GR 1996, 'Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells', Journal of Virology, vol. 70, no. 7, pp. 4502-4508.
Huang, Shuang ; Kamata, Tetsuji ; Takada, Yoshikazu ; Ruggeri, Zaverio M. ; Nemerow, Glen R. / Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells. In: Journal of Virology. 1996 ; Vol. 70, No. 7. pp. 4502-4508.
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