Adenovirus gene transfer causes inflammation in the brain

doi:10.1016/0306-4522(95)00068-T

Neuroscience

Volume 66, Issue 4, June 1995, Pages 1015-1024

https://doi.org/10.1016/0306-4522(95)00068-T Get rights and content

Abstract

We report that injecting an E1-deleted, non-replicating, human adenovirus type 5 vector into the brain leads to an inflammatory response. Much of this inflammation is induced directly by the virion particles themselves rather than through the expression of new proteins from the vector. The severity of inflammation was found to depend on the strain of inbred rat used: PVG rats have less inflammation than AO rats in response to a vector injection. Twelve hours after injection of adenovirus vectors into the striatum of AO rats, leukocytes were seen marginating to the walls of nearby blood vessels. By two days there was a large increase in major histocompatibility complex class I expression and a heavy infiltration of leukocytes, mainly macrophages and T cells. Retrograde transport of adenovirus to neurons of the substantia nigra was associated with a delayed and less intense inflammation at this distant site. Although AO and PVG rats showed comparable responses in the striatum up to six days, at later times PVG rats had less intense inflammation. In spite of the inflammatory response, vector-driven expression of the marker protein β-galactosidase and an adenovirus early protein was seen for at least two months following the injection, although expression declined with time.

The observation that adenovirus gene transfer leads to an inflammatory response in the brain must be taken into account when planning and interpreting experiments with these vectors. Furthermore, we conclude that using an appropriate strain of rat can diminish some aspects of the inflammation.

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Adenovirus gene transfer causes inflammation in the brain

Abstract

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Exp. Neurol.

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Molec. Immunol.

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Virology

Brain Res.

Adv. Immunol.

Trends Neurosci.

Virology

Exp. Neurol.

Transfer of a foreign gene into the brain using adenovirus vectors

Nature Genetics

Directin vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors

Nature Genetics

The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin

J. exp. Med.

Two subsets of rat T lymphocytes defined with monoclonal antibodies

Eur. J. Immunol.

Phenotype of rat natural killer cells defined by monoclonal antibodies marking rat lymphocyte subsets

Immunology

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J. Exp. Med.

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New Biol.

High-efficiency receptor-mediated delivery of small and large (48 kilobase) gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles

A model system forin vivo gene transfer into the central nervous system using an adenoviral vector

Nature Genetics

The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3

Immunology

Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses

Nature Genetics

Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver