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Functional changes in murine macrophages infected with cytomegalovirus relate to H-2-determined sensitivity to
P Price1, J G Winter, S Nikoletti
1Department of Microbiology, University of Western Australia.
Abstract:
Peritoneal macrophages were infected with murine cytomegalovirus in vitro, and indices of infection and macrophage function were monitored over 4 days. When the cells were assessed for the expression of viral antigen or for cytopathic effects, infection was found to be solely determined by the H-2 phenotype. Less than 10% of the macrophages from resistant H-2k strains were affected, whereas 90% of H-2d cells and approximately 80% of H-2b and H-2a cells became infected. Similar trends were demonstrable by the measurement of viral DNA. In H-2a cells (B10.A), Dd conferred sensitivity despite the resistant K and class II phenotype. The findings suggest a critical association between the class I antigens and an early stage in the infectious process. Indices of infection were paralleled by a loss of Fc receptor expression and optimal colloidal gold uptake, whereas most cells remained trypan blue negative, retained dehydrogenase and acid phosphatase activities, and did not release infectious virus during the period of study. This is consistent with a role for macrophages in the persistence of cytomegalovirus in the host.
Insights
Murine cytomegalovirus infection in macrophages depends on H-2 phenotype. Certain H-2 alleles confer resistance, while others like H-2d promote high infection rates, impacting macrophage function.
Area of Science:
- Immunology
- Virology
Background:
- Macrophages play a crucial role in host defense against viral infections.
- Murine cytomegalovirus (MCMV) is a model virus for studying herpesvirus-host interactions.
Purpose of the Study:
- To investigate the role of the H-2 major histocompatibility complex (MHC) phenotype in determining susceptibility of peritoneal macrophages to MCMV infection.
- To assess the impact of MCMV infection on macrophage function.
Main Methods:
- In vitro infection of murine peritoneal macrophages with MCMV.
- Assessment of viral antigen expression, cytopathic effects, and viral DNA levels.
- Monitoring of macrophage functions including Fc receptor expression, phagocytosis (colloidal gold uptake), cell viability (trypan blue exclusion), and enzyme activities (dehydrogenase, acid phosphatase).
Main Results:
- Macrophage susceptibility to MCMV infection was strongly correlated with the H-2 phenotype.
- H-2k strains showed resistance (<10% infection), while H-2d (approx. 90%), H-2b (approx. 80%), and H-2a (approx. 80%) strains were highly susceptible.
- Infection led to a loss of Fc receptor expression and reduced phagocytic capacity, but cells largely retained viability and enzymatic functions.
- The Dd locus conferred sensitivity in H-2a macrophages, indicating a role for class I MHC molecules.
Conclusions:
- The H-2 class I major histocompatibility complex phenotype critically influences an early stage of MCMV infection in macrophages.
- Macrophage dysfunction, including impaired Fc receptor function and phagocytosis, accompanies MCMV infection.
- Macrophages may contribute to the persistence of cytomegalovirus within the host.