Immunochemistry of adenoviruses

Limitations and new horizons of gene therapy

Balázs Stercz, Harry Perlstadt, K. Nagy, József Ongrádi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Adenoviruses have increasingly been recognized as significant viral pathogens causing highmorbidity andmortality especially among immunocompromised individuals such as transplant recipients and AIDS patients. Through the infection process, after the adenovirus fiber and penton are bonded to cell surface receptors through special amino acid moieties, secondary messengers activate protein kinases, pro-inflammatory cytokines and chemokines. Serotype and species specific antibodies also are induced. Recombinant human adenoviruses have been pivotal in the development of gene therapy strategies and have shown a great promise for the treatment of genetic disorders and malignancies. Recent studies have enlightened their harmful immunological effects dependent on fiber and hexon polypeptide structure and receptor binding. Pre-existing antibodies or those elicited by vectors neutralize input recombinant adenovirus particles rendering them ineffective. Mediators induce serious even lethal side effects and cytotoxic reactions which extinguish transgene expression. To overcome these difficulties new strategies are required in the application of recombinant adenoviruses to redirect vector entry from the natural receptors to alternative binding sites or using rare human or animal adenovirus fiber molecules to modify the native fiber structure by altering amino acid structure and creating chimeric fibers. This requires searching for, isolating and characterizing new serotypes, mutants or variants for new generation vectors. Human adenovirus 1 feline isolate (feline adenovirus) might fulfil these criteria.

Original languageEnglish
Pages (from-to)447-459
Number of pages13
JournalActa Microbiologica et Immunologica Hungarica
Volume60
Issue number4
DOIs
Publication statusPublished - Dec 1 2013

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Immunochemistry
Adenoviridae
Genetic Therapy
Human Adenoviruses
Felidae
Imino Acids
Inborn Genetic Diseases
Antibodies
Cell Surface Receptors
Transgenes
Chemokines
Protein Kinases
Acquired Immunodeficiency Syndrome
Binding Sites
Cytokines
Amino Acids
Peptides
Infection
Neoplasms

Keywords

  • feline adenovirus
  • gene therapy
  • modified fiber
  • neutralizing antibodies
  • pro-inflammatory cytokines
  • recombinant adenovirus vectors
  • redirected fiber attachment

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Immunochemistry of adenoviruses : Limitations and new horizons of gene therapy. / Stercz, Balázs; Perlstadt, Harry; Nagy, K.; Ongrádi, József.

In: Acta Microbiologica et Immunologica Hungarica, Vol. 60, No. 4, 01.12.2013, p. 447-459.

Research output: Contribution to journalArticle

Stercz, Balázs ; Perlstadt, Harry ; Nagy, K. ; Ongrádi, József. / Immunochemistry of adenoviruses : Limitations and new horizons of gene therapy. In: Acta Microbiologica et Immunologica Hungarica. 2013 ; Vol. 60, No. 4. pp. 447-459.
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