The coordinated activities of innate and adaptive immunity are critical for effective protection against viruses. To counter this, some viruses have evolved sophisticated strategies to circumvent immune cell recognition. In particular, cytomegaloviruses encode large arsenals of molecules that seek to subvert T cell and natural killer cell function via a remarkable array of mechanisms. Consequently, these ‘immunoevasins’ play a fundamental role in shaping the nature of the immune system by driving the evolution of new immune receptors and recognition mechanisms. Here, we review the diverse strategies adopted by cytomegaloviruses to target immune pathways and outline the host’s response.
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The authors acknowledge funding from the National Health and Medical Research Council of Australia to R.B. (APP1109901) and M.A.D-E. (GNT1119298), the Deutsche Forschungsgemeinschaft-funded research unit Advanced Concepts in Cellular Immune Control of Cytomegalovirus (FOR 2830) project ‘Solving the m04 paradox: evasion of missing-self recognition and CD8 T cell killing by MAT uORF’ to S.J. (JO 1634/1-1), the grant KK.01.1.1.01.0006, awarded to the Scientific Centre of Excellence for Virus Immunology and Vaccines and co-financed by the European Regional Development Fund, to S.J. and the Australian Research Council to J.R. (FL160100049).
Nature Reviews Immunology thanks A. Cerwenka and C. Biron for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Paired receptors
Closely related receptors that bind to the same or similar ligands but trigger opposing functional effects (for example, stimulatory versus inhibitory).
- V-type immunoglobulin domain
A compact protein module comprising two β-sheets arranged into a β-sandwich fold. 'V' refers to ‘variable’ indicating a subclass of immunoglobulin domains that possess nine β-strands and resemble those located within the variable portion of antibodies.
- ‘Missing-self’ recognition
A term used to describe how the downregulation of self-molecules, which act as ligands for inhibitory receptors, can trigger natural killer cell activation.
- Sec61 complex
A dynamic multiprotein channel that, in eukaryotic cells, is located within the endoplasmic reticulum membrane. It mediates the membrane insertion and translocation of most proteins that reside in the endomembrane system or are destined for secretion.
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Berry, R., Watson, G.M., Jonjic, S. et al. Modulation of innate and adaptive immunity by cytomegaloviruses. Nat Rev Immunol 20, 113–127 (2020). https://doi.org/10.1038/s41577-019-0225-5
Nature Reviews Immunology (2022)
Molecular and Cellular Biochemistry (2022)
Medical Microbiology and Immunology (2022)
Nature Reviews Microbiology (2021)