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Identification of a region of the virus genome involved in murine gammaherpesvirus 68-induced splenic pathology

Bahram Ebrahimi^1,

James P. Stewart^1,

¹ Laboratory for Clinical and Molecular Virology, Division of Veterinary Biomedical Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK
² Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK

Correspondence
Bernadette M. Dutia
B.M.Dutia{at}ed.ac.uk

Infection with the murine gammaherpesvirus MHV-68 has profound effects on splenic and mediastinal lymph node pathology in mice which lack the interferon- receptor (IFN- R^–/–). In these mice MHV-68 infection causes fibrosis and loss of lymphocytes in the spleen and the mediastinal lymph node as well as interstitial pulmonary fibrosis and fibrotic changes in the liver. The changes are associated with transient elevated latent virus loads in the spleen. Four independent virus mutants with insertions and/or deletions in the left end of the genome fail to induce the pathological changes and establish latency at normal levels in the spleen. The data indicate that the pathology does not correlate with any of the known genes encoded within this region of the genome, genes M1–M4 and the eight vtRNAs. Northern analysis of mRNAs transcribed by wild-type and mutant viruses shows that at least two uncharacterized transcripts are encoded within this region. These transcripts are absent in the mutant viruses and are candidates for the virus genes responsible for the aberrant pathology in IFN- R^–/– mice.

Present address: Department of Medical Microbiology, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.

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