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Dissecting the host response to a gamma-herpesvirus
P C Doherty1, J P Christensen, G T Belz
1Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. peter.doherty@stjude.org
Summary
Murine gamma-herpesvirus 68 (MHV-68) research reveals type I interferons control early replication, while CD4+ T cells limit viral persistence. MHV-68 uses immune evasion strategies, highlighting the importance of a comprehensive immune response for controlling large DNA viruses.
Area of Science:
- Virology
- Immunology
Background:
- Murine gamma-herpesvirus 68 (MHV-68) serves as a model for studying large DNA virus immunity and persistence in B lymphocytes.
- Genetically modified mice and MHV-68 mutants facilitate research into host-response elements and viral mechanisms.
Purpose of the Study:
- To dissect the immune response to MHV-68, focusing on the roles of type I interferons, CD4+ T cells, and CD8+ T cells.
- To investigate viral immune evasion strategies, including the function of the MHV-68 K3 protein and its impact on antigen presentation.
- To explore the relationship between lytic infection and viral latency, and to identify potential therapeutic targets.
Main Methods:
- Utilized genetically disrupted (-/-) mice lacking key host-response elements.
- Employed monoclonal antibody depletion protocols to assess the function of specific immune cells.
- Conducted mutational analysis of MHV-68, including studies on its encoded chemokine-binding protein and K3 protein.
- Examined the impact of immunization strategies on viral replication and latency.
Main Results:
- Type I interferons are crucial for early MHV-68 replication control.
- CD4+ T cells producing IFN-gamma are essential for limiting viral persistence.
- CD8+ T cells control the lytic phase but cannot prevent reactivation in CD4+ T-cell-deficient mice.
- The MHV-68 K3 protein impairs antigen presentation by MHC class I, potentially aiding immune evasion.
- Immunization targeting lytic phase epitopes limits replication but not latency.
- MHV-68 employs immune-subverting mechanisms like massive immunoglobulin response and MHC-independent T cell expansion.
Conclusions:
- A comprehensive immune response involving multiple components is vital for controlling persistent large DNA viruses like MHV-68.
- Understanding MHV-68's immune evasion strategies may offer insights into managing human herpesviruses such as Epstein-Barr virus and human herpesvirus-8.
- The MHV-68 model system provides valuable data for developing therapeutic interventions against persistent viral infections.