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Journal of Virology, November 2000, p. 9928-9936, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Recombinant Measles Viruses Efficiently Entering Cells through Targeted Receptors

Urs Schneider,1 Frances Bullough,2 Sompong Vongpunsawad,1 Stephen J. Russell,1 and Roberto Cattaneo1,*

Molecular Medicine Program, Mayo Foundation, Rochester, Minnesota 55905,1 and Cambridge Genetics, Cambridge 0CB4 OFG, United Kingdom2

Received 7 June 2000/Accepted 15 August 2000

We sought proof of principle that one of the safest human vaccines, measles virus Edmonston B (MV-Edm), can be genetically modified to allow entry via cell surface molecules other than its receptor CD46. Hybrid proteins consisting of the epidermal growth factor (EGF) or the insulin-like growth factor 1 (IGF1) linked to the extracellular (carboxyl) terminus of the MV-Edm attachment protein hemagglutinin (H) were produced. The standard H protein gene was replaced by one coding for H/EGF or H/IGF1 in cDNA copies of the MV genome. Recombinant viruses were rescued and replicated to titers approaching those of the parental strain. MV displaying EGF or IGF1 efficiently entered CD46-negative rodent cells expressing the human EGF or the IGF1 receptor, respectively, and the EGF virus caused extensive syncytium formation and cell death. Taking advantage of a factor Xa protease recognition site engineered in the hybrid H proteins, the displayed domain was cleaved off from virus particles, and specific entry in rodent cells was abrogated. These studies prove that MV can be engineered to selectively eliminate cells expressing a targeted receptor and provide insights into the mechanism of MV entry.

* Corresponding author. Mailing address: Molecular Medicine Program, Mayo Foundation, Guggenheim 18, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-0171. Fax: (507) 266-2122. E-mail: cattaneo.roberto{at}mayo.edu.

Journal of Virology, November 2000, p. 9928-9936, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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