Disruption of the M2 Gene of Murine Gammaherpesvirus 68 Alters Splenic Latency following Intranasal, but Not Intraperitoneal, Inoculation
Open Access
- 15 February 2002
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 76 (4), 1790-1801
- https://doi.org/10.1128/jvi.76.4.1790-1801.2002
Abstract
Infection of mice with murine gammaherpesvirus 68 (γHV68; also referred to as MHV68) provides a tractable small-animal model with which to address the requirements for the establishment and maintenance of gammaherpesvirus infection in vivo. The M2 gene of γHV68 is a latency-associated gene that encodes a protein lacking discernible homology to any known viral or cellular proteins. M2 gene transcripts have been detected in latently infected splenocytes (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999; H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999) and peritoneal exudate cells (H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999), as well as in a latently γHV68-infected B-lymphoma cell line (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999). Here we describe the generation of γHV68 mutants with disruptions in the M2 gene. Mutation of the M2 gene did not affect the ability of the virus to replicate in tissue culture, nor did it affect γHV68 virulence in B6.Rag1 deficient mice. However, we found that M2 was differentially required for acute replication in vivo. While mutation of M2 did not affect acute phase of virus replication in the lungs of mice following intranasal inoculation, acute-phase virus replication in the spleen was decreased compared to that of the wild-type and marker rescue viruses following intraperitoneal inoculation. Upon intranasal inoculation, M2 mutant viruses exhibited a significant decrease in the establishment of latency in the spleen on day 16 postinfection, as measured by the frequency of viral genome-positive cells. In addition, M2 mutant viral genome-positive cells reactivated from latency inefficiently compared to wild-type and marker rescue viruses. By day 42 after intranasal inoculation, the frequencies of M2 mutant and wild-type viral genome-positive cells were nearly equivalent and little reactivation was detected from either population. In sharp contrast to the results obtained following intranasal inoculation, after intraperitoneal inoculation, no significant defect was observed in the establishment or reactivation from latency with the M2 mutant viruses. These results indicate that the requirements for the establishment of latency are affected by the route of infection.Keywords
This publication has 44 references indexed in Scilit:
- Unraveling immunity to γ-herpesviruses: a new model for understanding the role of immunity in chronic virus infectionCurrent Opinion in Immunology, 1999
- Host and viral genetics of chronic infection: a mouse model of gamma-herpesvirus pathogenesisCurrent Opinion in Microbiology, 1999
- Absence of splenic latency in murine gammaherpesvirus 68-infected B cell-deficient miceJournal of General Virology, 1996
- Murine gammaherpesvirus-induced splenomegaly: a critical role for CD4 T cellsJournal of General Virology, 1996
- Interactions of the murine gammaherpesvirus with the immune systemCurrent Opinion in Immunology, 1994
- Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivoJournal of General Virology, 1992
- Virological and pathological features of mice infected with murine gammaherpesvirus 68Journal of General Virology, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992
- Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiriJournal of General Virology, 1990
- Cloning and molecular characterization of the murine herpesvirus 68 genomeJournal of General Virology, 1990