Tinkering with a viral ribonucleotide reductase
1Department of Clinical and Biological Sciences, University of Turin, S Luigi Gonzaga Hospital, Orbassano, Turin, Italy. david.lembo@unito.it
Trends in Biochemical Sciences
|November 8, 2008
Summary
Murine cytomegalovirus M45, a viral enzyme, lost its original function but now inhibits a cellular protein to block immune responses. This discovery reveals a novel viral immune evasion strategy and supports evolutionary tinkering.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Ribonucleotide reductase (RNR) is essential for DNA synthesis and present in most organisms and viruses.
- Beta-herpesvirus RNR R1 subunits are catalytically inactive, their function being previously unknown.
- Murine cytomegalovirus (MCMV) encodes the M45 protein, a homologue of the RNR R1 subunit.
Purpose of the Study:
- To elucidate the enigmatic function of beta-herpesvirus RNR R1 subunit homologues.
- To investigate the role of the MCMV M45 protein in viral pathogenesis and host interaction.
Main Methods:
- Analysis of M45 protein function in the context of MCMV infection.
- Investigating the interaction of M45 with cellular proteins, specifically RIP1.
- Assessing the impact of M45 on cellular signaling pathways related to innate immunity and inflammation.
Main Results:
- M45 protein lacks catalytic activity associated with canonical RNR.
- M45 inhibits RIP1, a cellular adaptor protein involved in immune signaling.
- Inhibition of RIP1 by M45 effectively blocks cellular pathways crucial for innate immunity and inflammation.
Conclusions:
- MCMV M45 has evolved a novel mechanism to subvert host innate immunity.
- Viral RNR homologues can acquire new functions through evolutionary processes.
- This finding highlights the concept of evolutionary tinkering in viral adaptation and immune evasion.
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