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Differential Role OF α vβ 3 and α vβ 5 Integrins in Iinternalization and Transduction Efficacies of Wild Type and RGD4C Fiber-modified Adenoviruses


Majhen, Dragomira; Nemet, Josip; Richardson, Jennifer; Gabrilovac, Jelka; Hajsig, Martina; Osmak, Maja; Eloit, Marc; Ambriović-Ristov, Andreja
Differential Role OF α vβ 3 and α vβ 5 Integrins in Iinternalization and Transduction Efficacies of Wild Type and RGD4C Fiber-modified Adenoviruses // Virus Research, 139 (2009), 1; 64-73 (međunarodna recenzija, članak, znanstveni)


Naslov
Differential Role OF α vβ 3 and α vβ 5 Integrins in Iinternalization and Transduction Efficacies of Wild Type and RGD4C Fiber-modified Adenoviruses

Autori
Majhen, Dragomira ; Nemet, Josip ; Richardson, Jennifer ; Gabrilovac, Jelka ; Hajsig, Martina ; Osmak, Maja ; Eloit, Marc ; Ambriović-Ristov, Andreja

Izvornik
Virus Research (0168-1702) 139 (2009), 1; 64-73

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Adenovirus; α vβ 3 integrin; α vβ 5 integrin; transduction; internalization; fiber; RGD4C

Sažetak
In order to analyze the role of α vβ 3 and α vβ 5 integrins in gene transfer by adenovirus-based vectors, an RGD4C motif was inserted into the HI-loop of wild type or shortened fiber protein of human adenovirus of serotype 5, thereby creating Ad5RGD4C and Ad5 639RGD4C vectors, respectively. Infection by the latter is independent of the coxsackie adenovirus receptor. Internalization of these vectors and transduction were investigated in several stably transfected cell clones derived from a human laryngeal carcinoma cell line (HEp2) expressing different ratios of α vβ 5 and α vβ 3 integrins. We show that α vβ 3 is more successful than α vβ 5 in: (i) mediating adenovirus internalization and transduction when the RGD motif is present only in the penton base (ii) mediating internalization and transduction by RGD4C-fiber modified adenoviruses. The highest amount of internalized virus was found in the cell clone in which α vβ 3 integrin predominated over α vβ 5 integrin (as judged by the % of cells expressing α vβ 3 and α vβ 5 integrins). However the level of transgene expression in this cell line was even lower than that in parental HEp2 cells which do not express α vβ 3 integrin. This discrepancy between internalization and transgene expression (transduction) is likely due to the crucial role of α vβ 5 in membrane permeabilization, indicating that α vβ 5 is a limiting factor for Ad5-mediated gene transfer. We conclude that α vβ 3 integrin is an efficient adenovirus internalization receptor, but cannot functionally replace α vβ 5 in endosomal release.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
098-0982464-2520 - ULOGA MEMBRANSKIH PEPTIDAZA NA TUMORSKIM I NORMALNIM STANICAMA (Jelka Gabrilovac, )
098-0982913-2748 - Stanični odgovor na citotoksične spojeve i razvoj otpornosti (Maja Osmak, )
098-0982913-2850 - Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike (Andreja Ambriović Ristov, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE