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Journal of Virology, January 2007, p. 639-649, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01089-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo{triangledown}

Yung-Wei Pan,1 Jarrad M. Scarlett,1 Tammy T. Luoh,1 and Peter Kurre1,2*

Departments of Pediatrics,1 Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon2

Received 26 May 2006/ Accepted 27 September 2006

Human immunodeficiency virus type 1-derived lentivirus vectors bearing the vesicular stomatitis virus G (VSV-G) envelope glycoprotein demonstrate a wide host range and can stably transduce quiescent hematopoietic stem cells. In light of concerns about biosafety and potential germ line transmission, they have been used predominantly for ex vivo strategies, thought to ensure the removal of excess surface-bound particles and prevent in vivo dissemination. Studies presented here instead reveal prolonged particle adherence after ex vivo exposure, despite serial wash procedures, with subsequent transduction of secondary target cells in direct and transwell cocultures. We explored the critical parameters affecting particle retention and transfer and show that attachment to the cell surface selectively protects virus particles from serum complement-mediated inactivation. Moreover, studies with nonmyeloablated murine recipients show that transplantation of vector-exposed, washed hematopoietic cells results in systemic dissemination of functional VSV-G/lentivector particles. We demonstrate genetic marking by inadvertent transfer of vector particles and prolonged expression of transgene product in recipient tissues. Our findings have implications for biosafety, vector design, and cell biology research.

* Corresponding author. Mailing address: 3181 SW Sam Jackson Park Road, Oregon Health and Science University, Division of Pediatric Hematology/Oncology, CDRCP, Portland, OR 97239. Phone: (503) 494-0829. Fax: (503) 494-0714. E-mail: kurrepe{at}ohsu.edu.

{triangledown} Published ahead of print on 11 October 2006.

Journal of Virology, January 2007, p. 639-649, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01089-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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