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Updated: Aug 15, 2026
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules
Nicolas Collin1, Jean-Luc Guérin, Ingo Drexler
1UMR 1225 Interactions Hôtes Agents pathogènes, INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, BP87614, 31076 Toulouse cedex 03, France.
Abstract:
Downregulation of MHC class I molecules is a strategy developed by some viruses to escape cellular immune responses. Myxoma virus (MV), a poxvirus causing rabbit myxomatosis, encodes MV-LAP that is known to increase MHC-I endocytosis and degradation through a C(4)HC(3) motif critical for an E3 ubiquitin ligase activity. Here, we performed a functional mapping of MV-LAP and showed that not only the C(4)HC(3) motif is necessary for a marked downregulation of MHC-I but also a conserved region in the C-terminal part of the protein. We also showed that the putative transmembrane domains are responsible for a specific subcellular localization of the protein: they retain MV-LAP in the ER in transfected cells and in the endolysosomal compartments in infected cells. We observed that a specific MV infection context is necessary for a fully efficient downregulation of MHC-I. Our data suggest that the functionality of viral LAP factors, inherited by herpes- and poxviruses from mammalian cells, is more complex than anticipated.
Insights
Myxoma virus (MV) protein MV-LAP downregulates MHC class I molecules to evade immune responses. Functional mapping reveals a C-terminal region, alongside the E3 ubiquitin ligase motif, is crucial for this immune evasion strategy.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Viruses employ strategies to evade host immune responses, including downregulating MHC class I molecules.
- Myxoma virus (MV), a poxvirus, utilizes the MV-LIP protein, which possesses E3 ubiquitin ligase activity via a C(4)HC(3) motif, to enhance MHC-I endocytosis and degradation.
Purpose of the Study:
- To functionally map the Myxoma virus LAP (MV-LAP) protein and elucidate its role in MHC class I downregulation.
- To identify specific protein domains and cellular contexts essential for MV-LAP's immune evasion function.
Main Methods:
- Functional mapping of the MV-LAP protein.
- Analysis of MHC class I downregulation in transfected and infected cells.
- Investigation of protein localization using subcellular fractionation.
Main Results:
- The C(4)HC(3) motif and a conserved C-terminal region of MV-LAP are both necessary for significant MHC class I downregulation.
- Transmembrane domains dictate MV-LAP's subcellular localization, retaining it in the ER in transfected cells and endolysosomal compartments during infection.
- Efficient MHC class I downregulation requires a specific MV infection context.
Conclusions:
- The functionality of viral LAP factors is more complex than previously understood.
- MV-LAP utilizes multiple domains and specific cellular environments for effective immune evasion.
- These findings provide insights into poxvirus strategies for subverting host immunity.
