beta-Arrestins modulate Adenovirus-vector-induced innate immune responses: differential regulation by beta-arrestin-1 and beta-arrestin-2

Virus Res. 2010 Jan;147(1):123-34. doi: 10.1016/j.virusres.2009.10.023. Epub 2009 Nov 6.


Adenovirus (Ad)-based vectors have been utilized in human gene transfer clinical trials since 1993. Unfortunately, innate immune responses directed against the Ad capsid and/or its genetic cargo can significantly limit the usage of Ad vectors. Previous studies have demonstrated that several signaling pathways are triggered by Ads, inclusive of TLR-dependent pathways. The G-protein-coupled receptor adaptors beta-arrestin-1 (beta-Arr1) and beta-arrestin-2 (beta-Arr2) are known to have pivotal roles in regulating TLR4 triggered signaling and inflammatory responses. In this study, we examined the role of beta-arrestins in Ad5-vector-induced inflammatory responses. Our studies reveal that both beta-arrestins are capable of modulating Ad5-vector-induced inflammatory responses in vivo and in vitro. Importantly, our studies divulge another level of complexity to these responses, as our results demonstrate beta-Arr1 to be a positive regulator, and beta-Arr2 a negative regulator of Ad5 induced innate immune responses. These data may allow gene therapy biologists to more accurately study the mechanisms underlying Ad5-vector-induced immune responses, and may also direct future efforts to modulate these mechanisms to improve the safety and/or efficacy of this important gene transfer vector.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology*
  • Adenoviruses, Human / immunology*
  • Animals
  • Arrestins / immunology*
  • Cytokines / biosynthesis
  • Gene Expression Regulation*
  • Genetic Vectors*
  • Immunomodulation*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / virology
  • Mice
  • Mice, Inbred C57BL
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins


  • ARRB1 protein, human
  • ARRB2 protein, human
  • Arrb1 protein, mouse
  • Arrb2 protein, mouse
  • Arrestins
  • Cytokines
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins