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Journal of Virology, September 2009, p. 8713-8721, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00741-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Previously Unrecognized Amino Acid Substitutions in the Hemagglutinin and Fusion Proteins of Measles Virus Modulate Cell-Cell Fusion, Hemadsorption, Virus Growth, and Penetration Rate{triangledown}

Hiromi Okada,1 Masae Itoh,2 Kyosuke Nagata,1 and Kaoru Takeuchi1*

Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan,1 Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan2

Received 10 April 2009/ Accepted 17 June 2009

Wild-type measles virus (MV) isolated in B95a cells could be adapted to Vero cells after several blind passages. In this study, we have determined the complete nucleotide sequences of the genomes of the wild type (T11wild) and its Vero cell-adapted (T11Ve-23) MV strain and identified amino acid substitutions R516G, E271K, D439E and G464W (D439E/G464W), N481Y/H495R, and Y187H/L204F in the nucleocapsid, V, fusion (F), hemagglutinin (H), and large proteins, respectively. Expression of mutated H and F proteins from cDNA revealed that the H495R substitution, in addition to N481Y, in the H protein was necessary for the wild-type H protein to use CD46 efficiently as a receptor and that the G464W substitution in the F protein was important for enhanced cell-cell fusion. Recombinant wild-type MV strains harboring the F protein with the mutations D439E/G464W [F(D439E/G464W)] and/or H(N481Y/H495R) protein revealed that both mutated F and H proteins were required for efficient syncytium formation and virus growth in Vero cells. Interestingly, a recombinant wild-type MV strain harboring the H(N481Y/H495R) protein penetrated slowly into Vero cells, while a recombinant wild-type MV strain harboring both the F(D439E/G464W) and H(N481Y/H495R) proteins penetrated efficiently into Vero cells, indicating that the F(D439E/G464W) protein compensates for the inefficient penetration of a wild-type MV strain harboring the H(N481Y/H495R) protein. Thus, the F and H proteins synergistically function to ensure efficient wild-type MV growth in Vero cells.

* Corresponding author. Mailing address: Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Phone and fax: 81 29 853 3472. E-mail: ktakeuch{at}md.tsukuba.ac.jp

{triangledown} Published ahead of print on 24 June 2009.

Journal of Virology, September 2009, p. 8713-8721, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00741-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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