Variation in adenovirus receptor expression and adenovirus vector-mediated transgene expression at defined stages of the cell cycle. Academic Article uri icon

Overview

MeSH

  • Antigens, CD
  • Aphidicolin
  • Capsid
  • Carcinoma
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Cyclin B1
  • Gene Expression
  • Gene Transfer Techniques
  • Integrin alphaV
  • Lung Neoplasms
  • Nocodazole
  • Paclitaxel
  • Transgenes
  • Tumor Cells, Cultured

MeSH Major

  • Adenoviridae
  • Cell Cycle
  • Cyclin B
  • Genetic Vectors
  • Receptors, Virus

abstract

  • Detailed investigations have addressed the infection pathway of recombinant adenovirus (Ad) gene transfer vectors, but little attention has been paid to the influence of cell physiology on the outcome of Ad infection. Based on observations that Ad infection of clonal cell populations show cell-to-cell variability in the extent of capsid binding, we hypothesized that the cell cycle may influence the outcome of Ad infection. To address this hypothesis, we evaluated Ad association with cells in both unsynchronized and pharmacologically synchronized cell populations. In unsynchronized cell populations, elevated Ad association with cells correlated with expression of cyclin B1, a marker of entry into the M phase of mitosis. The same analysis conducted on cell populations that were synchronized at M phase (using paclitaxel or nocodazole) or at S phase (using aphidicolin) confirmed that M phase cells bound three- to sixfold more capsid compared with unsynchronized cells, which are primarily in the G(1) and G(2) phases. The elevated association of vectors with cells translated into 2.5- to 4-fold greater transgene expression 24 hours after infection. Assessment of cell surface expression of Ad receptors demonstrated that both the high-affinity coxsackie-adenovirus receptor for Ad fiber protein and the low-affinity alpha(v) integrin receptor for Ad penton base protein showed increased cell surface expression at M phase (1.5-fold and 2- to 3-fold increases, respectively). These data demonstrate that Ad infection of a homogenous population of cells can vary depending on the cell cycle stage, with enhanced Ad binding and expression correlating with the enhanced expression of Ad receptors during M phase. These observations have relevance to understanding the mechanisms of gene transfer by Ad vectors and should help in the design of in vivo gene transfer strategies.

publication date

  • July 2001

has subject area

  • Adenoviridae
  • Antigens, CD
  • Aphidicolin
  • Capsid
  • Carcinoma
  • Cell Cycle
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Cyclin B
  • Cyclin B1
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors
  • Integrin alphaV
  • Lung Neoplasms
  • Nocodazole
  • Paclitaxel
  • Receptors, Virus
  • Transgenes
  • Tumor Cells, Cultured

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/mthe.2001.0414

PubMed ID

  • 11472101

Additional Document Info

start page

  • 13

end page

  • 21

volume

  • 4

number

  • 1