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Simplexviruses Successfully Adapt to Their Host by Fine-Tuning Immune Responses
Alessandra Mozzi1, Rachele Cagliani1, Chiara Pontremoli1
1Scientific Institute, IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy.
Molecular Biology and Evolution
|June 22, 2022
Summary
Primate herpes simplex viruses (HSV) adapt to hosts, with B virus causing severe human disease. Evolution of HSV-1/HSV-2 ICP47 shows loss of immune suppression, unlike B virus, potentially explaining disease severity.
Area of Science:
- Virology
- Evolutionary Biology
- Immunology
Background:
- Primate herpes simplex viruses (HSV) are host-specific and generally benign.
- Cross-species transmission, like macacine herpesvirus 1 (B virus) to humans, can cause severe illness.
- Understanding viral adaptation to hosts is crucial for predicting disease outcomes.
Purpose of the Study:
- To investigate genome-wide adaptation signals in simplexviruses infecting hominins.
- To functionally characterize evolutionary changes in viral immune evasion strategies.
- To explore the role of specific viral proteins in host-pathogen interactions and disease severity.
Main Methods:
- Genome-wide scan for positive selection in primate simplexviruses.
- In vitro expression and functional analysis of herpes simplex virus (HSV) ICP47 mutants.
- Assessing the impact of viral protein variants on host immune molecule expression (MHC class I, HLA-G).
Main Results:
- Episodic positive selection identified in three viral glycoproteins and immune-escape genes.
- Herpes simplex virus (HSV)-1/HSV-2 ICP47, unlike B virus ICP47, can up-regulate Human Leukocyte Antigen (HLA)-G.
- Specific amino acid residues in ICP47 are sufficient to determine HLA-G up-regulation, indicating a loss of immunosuppression in HSV-1/HSV-2 evolution.
Conclusions:
- Evolutionary changes in HSV ICP47 have shifted its function from immunosuppression to immune stimulation (HLA-G up-regulation).
- These viral adaptations may explain the differential pathogenicity of B virus compared to HSV-1/HSV-2 in humans.
- Simplexviruses dynamically modulate host immune pathways for successful host adaptation and persistence.
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