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Journal of Virology, August 2005, p. 10369-10375, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10369-10375.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of Neuraminidase-Resistant Mutants Derived from Rotavirus Porcine Strain OSU

José Agustín López,^1, Antonio José Maldonado,¹ Marlene Gerder,¹ José Abanero,² Juan Murgich,² Flor H. Pujol,¹ Ferdinando Liprandi,¹ and Juan Ernesto Ludert^1*

Centro de Microbiología y Biología Celular,¹ Centro de Química, Instituto Venezolano de Investigaciones Científicas, Caracas 1020-A, Venezuela²

Received 5 March 2005/ Accepted 2 May 2005

Infection by some rotavirus strains requires the presence of sialic acid on the cell surface, its infectivity being reduced in cells treated with neuraminidase. A neuraminidase treatment-resistant mutant was isolated from the porcine rotavirus strain OSU. In reassortant strains, the neuraminidase-resistant phenotype segregated with the gene coding for VP4. The mutant retained its capacity to bind to sialic acid. The VP4 sequence of the mutant differed from that of the parental OSU strain in an Asp-to-Asn substitution at position 100. Neutralization escape mutants selected from an OSU neuraminidase-sensitive clone by monoclonal antibodies that failed to recognize the neuraminidase-resistant mutant strain carried the same mutation at position 100 and were also neuraminidase resistant. Neuraminidase sensitivity was restored when the mutation at position 100 was compensated for by a second mutation (Gln to Arg) at position 125. Molecular mechanics simulations suggest that the neuraminidase-resistant phenotype associated with mutation of OSU residue 100 from Asp to Asn reflects the conformational changes of the sialic acid cleft that accompany sialic acid binding.

Present address: Laboratorio de Microbiología, Decanato de Ciencias Veterinarias, Universidad Centro Occidental Lisandro Alvarado, Barquisimeto, Venezuela.