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Journal of Virology, September 2003, p. 9700-9709, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9700-9709.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Murid Herpesvirus 4 Strain 68 M2 Protein Is a B-Cell-Associated Antigen Important for Latency but Not Lymphocytosis

Alastair I. Macrae,1 Edward J. Usherwood,2 S. Mazher Husain,3 Emilio Flaño,4 In-Jeong Kim,4 David L. Woodland,4 Anthony A. Nash,1 Marcia A. Blackman,4 Jeffery T. Sample,3,5 and James P. Stewart6*

Department of Medical Microbiology and Genitourinary Medicine, Centre for Comparative Infectious Diseases, University of Liverpool, Liverpool,6 Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh, United Kingdom,1 Department of Microbiology and Immunology, Dartmouth College Medical School, Hanover, New Hampshire,2 Department of Biochemistry, St. Jude Children's Research Hospital,3 Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee,5 The Trudeau Institute, Saranac Lake, New York4

Received 3 March 2003/ Accepted 10 June 2003

This work describes analyses of the function of the murid herpesvirus 4 strain 68 (MHV-68) M2 gene. A frameshift mutation was made in the M2 open reading frame that caused premature termination of translation of M2 after amino acid residue 90. The M2 mutant showed no defect in productive replication in vitro or in lungs after infection of mice. Likewise, the characteristic transient increase in spleen cell number, Vß4 T-cell-receptor-positive CD8+ T-cell mononucleosis, and establishment of latency were unaffected. However, the M2 mutant virus was defective in its ability to cause the transient sharp rise in latently infected cells normally seen in the spleen after infection of mice. We also demonstrate that expression of M2 is restricted to B cells in the spleen and that M2 encodes a 30-kDa protein localizing predominantly in the cytoplasm and plasma membrane of B cells.

* Corresponding author. Mailing address: Department of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, United Kingdom. Phone: 44 151 794 7596. Fax: 44 151 706 5805. E-mail: j.p.stewart{at}liv.ac.uk.

Journal of Virology, September 2003, p. 9700-9709, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9700-9709.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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