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Immunogenicity in Mice of Human Metapneumovirus With a Truncated SH Glycoprotein

Lookup NU author(s): Dr Alison Tedcastle, Fiona Fenwick, Emeritus Professor Geoffrey Toms

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Abstract

The SH glycoprotein of human metapneumovirus (HMPV) is twice the size of that of human respiratory syncytial virus and possesses a large, hydrophilic luminal domain. The glycoprotein is located on the surface of the virion and of virus infected cells and, if immunogenic, might be expected to play a role in anti-viral immunity. Initial attempts to study anti-SH antibody immunogenicity were thwarted by the instability of the SH gene on passage both in human bronchial epithelial cells and in mice. Repeated passage of virus isolates in human bronchial epithelial cells in culture resulted in the appearance and eventual predominance of HMPV mutants lacking all or most of the luminal domain of SH coincidental with the loss of productive infection in mouse lungs. Where infection was established in mice with an early cell culture passage, the virus recovered from mouse lung differed markedly from the inoculum, carrying 19 coding mutations in the SH luminal domain. Immunization of mice with a mutant virus variant expressing only 14 amino acids of the luminal domain of SH induced a cross-reactive antibody response to both the F glycoprotein and the SH glycoprotein but a largely sub-group specific response to the G glycoprotein. Similar patterns of response were achieved by immunization with individual HMPV glycoproteins expressed from recombinant vaccinia viruses. Recombinant truncated SH glycoprotein induced sub-group cross-reactive antibodies capable of neutralizing wild-type virus. Recombinant F glycoprotein also induced cross-reactive neutralizing antibodies whilst recombinant G glycoprotein induced largely strain-specific, non-neutralizing antibodies. J. Med. Virol. 86:547-557, 2014. (c) 2013 Wiley Periodicals, Inc.

Publication metadata

Author(s): Tedcastle AB, Fenwick F, Robinson MJ, Toms GL

Publication type: Article

Publication status: Published

Journal: Journal of Medical Virology

Year: 2014

Volume: 86

Issue: 4

Pages: 547-557

Print publication date: 01/04/2014

Online publication date: 05/12/2013

Acceptance date: 12/07/2013

ISSN (print): 0146-6615

ISSN (electronic): 1096-9071

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1002/jmv.23731

DOI: 10.1002/jmv.23731

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