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Alteration of host defense mechanisms by murine cytomegalovirus infection
Abstract:
An animal model of a sublethal infection, utilizing murine cytomegalovirus (MCMV), was developed to determine whether immunological factors could contribute to the establishment of a persistent viral infection. Adult female C3H mice inoculated intraperitoneally with 10(5) plaque-forming units of MCMV developed splenomegaly 5 to 12 days after infection. Virus replicated to peak titers (10(3) to 10(6) plaque-forming units per g of tissue) in liver, spleen, lung, kidney, and salivary gland tissue during the acute phase of the infection (3 to 12 days); it then decreased to undetectable levels in all tissues except salivary gland. Serum interferon was detected as early as 12 h after infection, peaked at 36 h (1,093 U/ml), and was undetectable by 4 days after infection. MCMV-infected animals were hyporeactive to interferon induction with New castle disease virus on days 5 to 9 of the infection. Splenic lymphocyte reactivity to phytohemagglutinin and lipopolysaccharide was normal early during the course of the infection, was suppressed during the acute phase of the infection, and had returned to normal by day 18. These data indicate that several parameters of host defense are transiently suppressed during the course of a MCMV infection. The capacity of cytomegaloviruses to alter host resistance may be one factor that contributes to the establishment of a persistent infection.
Insights
Murine cytomegalovirus (MCMV) infection transiently suppresses host immune defenses in mice. This immune suppression may enable the virus to establish a persistent infection, particularly in salivary glands.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Persistent viral infections pose significant health challenges.
- Murine cytomegalovirus (MCMV) serves as a model for studying persistent herpesvirus infections.
- Understanding the interplay between host immunity and viral persistence is crucial.
Purpose of the Study:
- To investigate the role of immunological factors in the establishment of persistent MCMV infection.
- To characterize the immune response during a sublethal MCMV infection in a murine model.
Main Methods:
- Adult female C3H mice were inoculated with a sublethal dose of MCMV.
- Viral titers were measured in various tissues.
- Serum interferon levels and splenic lymphocyte reactivity were assessed.
Main Results:
- MCMV replicated in multiple organs during the acute phase, with persistence primarily in salivary glands.
- A transient suppression of host immune responses, including interferon production and lymphocyte reactivity, was observed.
- Mice showed hyporeactivity to interferon induction during the acute infection phase.
Conclusions:
- Transient suppression of host defense mechanisms during MCMV infection is evident.
- Altered host resistance by cytomegaloviruses may contribute to the establishment of persistent infections.
- This animal model provides insights into the pathogenesis of persistent viral infections.