Identification of adenovirus serotype 5 hexon regions that interact with scavenger receptors

Reeti Khare, Vijay S. Reddy, Glen R. Nemerow, Michael A Barry

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Most of an intravenous dose of species C adenovirus serotype 5 (Ad5) is destroyed by liver Kupffer cells. In contrast, another species C virus, Ad6, evades these cells to mediate more efficient liver gene delivery. Given that this difference in Kupffer cell interaction is mediated by the hypervariable (HVR) loops of the virus hexon protein, we genetically modified each of the seven HVRs of Ad5 with a cysteine residue to enable conditional blocking of these sites with polyethylene glycol (PEG). We show that these modifications do not affect in vitro virus transduction. In contrast, after intravenous injection, targeted PEGylation at HVRs 1, 2, 5, and 7 increased viral liver transduction up to 20-fold. Elimination or saturation of liver Kupffer cells did not significantly affect this increase in the liver transduction. In vitro, PEGylation blocked uptake of viruses via the Kupffer cell scavenger receptor SRA-II. These data suggest that HVRs 1, 2, 5, and 7 of Ad5 may be involved in Kupffer cell recognition and subsequent destruction. These data also demonstrate that this conditional genetic-chemical mutation strategy is a useful tool for investigating the interactions of viruses with host tissues.

Original languageEnglish (US)
Pages (from-to)2293-2301
Number of pages9
JournalJournal of Virology
Volume86
Issue number4
DOIs
StatePublished - Feb 2012

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Kupffer cells
Scavenger Receptors
Adenoviridae
Kupffer Cells
serotypes
Viruses
viruses
receptors
Liver
liver
hepatocytes
polyethylene glycol
gene transfer
intravenous injection
Intravenous Injections
Cell Communication
Cysteine
cysteine
Serogroup
mutation

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Identification of adenovirus serotype 5 hexon regions that interact with scavenger receptors. / Khare, Reeti; Reddy, Vijay S.; Nemerow, Glen R.; Barry, Michael A.

In: Journal of Virology, Vol. 86, No. 4, 02.2012, p. 2293-2301.

Research output: Contribution to journalArticle

Khare, Reeti ; Reddy, Vijay S. ; Nemerow, Glen R. ; Barry, Michael A. / Identification of adenovirus serotype 5 hexon regions that interact with scavenger receptors. In: Journal of Virology. 2012 ; Vol. 86, No. 4. pp. 2293-2301.
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