Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver
- 1 May 2007
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (9), 4866-4871
- https://doi.org/10.1128/jvi.02819-06
Abstract
Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration and degradation. After i.v. administration, Ad5 rapidly binds to circulating platelets, which causes their activation/aggregation and subsequent entrapment in liver sinusoids. Virus-platelet aggregates are taken up by Kupffer cells and degraded. Ad sequestration in organs can be reduced by platelet depletion prior to vector injection. Identification of this new sequestration mechanism and construction of vectors that avoid it could improve levels of target cell transduction at lower vector doses.Keywords
This publication has 59 references indexed in Scilit:
- Influence of Coagulation Factor Zymogens on the Infectivity of Adenoviruses Pseudotyped with Fibers from Subgroup DJournal of Virology, 2007
- Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearanceBlood, 2006
- Adenovirus Type 5 Interactions with Human Blood Cells May Compromise Systemic DeliveryMolecular Therapy, 2006
- Adenovirus Binding to Blood Factors Results in Liver Cell Infection and HepatotoxicityJournal of Virology, 2005
- Titer determination of Ad5 in blood: a cautionary noteGene Therapy, 2003
- Adenovirus Serotype 5 Fiber Shaft InfluencesIn VivoGene Transfer in MiceHuman Gene Therapy, 2003
- Adenoviral Vectors Do Not Induce, Inhibit, or Potentiate Human Platelet AggregationHuman Gene Therapy, 2002
- Early Platelet Aggregation as a Cause of Thrombocytopenia in Classical Swine FeverVeterinary Pathology, 2002
- Fatal Disseminated Adenoviral Infection Associated with Thrombotic Thrombocytopenic Purpura after Allogeneic Bone Marrow TransplantationLeukemia & Lymphoma, 2001
- Platelet phagocytosis in the spleen of patients with idiopathic thrombocytopenic purpura (ITP)Histopathology, 1980