Oligomerization and Cell Egress Controlled by Two Microdomains of Canine Distemper Virus Matrix Protein.

Gast, Matthieu; Kadzioch, Nicole P.; Milius, Doreen; Origgi, Francesco; Plattet, Philippe (2021). Oligomerization and Cell Egress Controlled by Two Microdomains of Canine Distemper Virus Matrix Protein. mSphere, 6(2) American Society for Microbiology 10.1128/mSphere.01024-20

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The multimeric matrix (M) protein of clinically relevant paramyxoviruses orchestrates assembly and budding activity of viral particles at the plasma membrane (PM). We identified within the canine distemper virus (CDV) M protein two microdomains, potentially assuming α-helix structures, which are essential for membrane budding activity. Remarkably, while two rationally designed microdomain M mutants (E89R, microdomain 1 and L239D, microdomain 2) preserved proper folding, dimerization, interaction with the nucleocapsid protein, localization at and deformation of the PM, the virus-like particle formation, as well as production of infectious virions (as monitored using a membrane budding-complementation system), were, in sharp contrast, strongly impaired. Of major importance, raster image correlation spectroscopy (RICS) revealed that both microdomains contributed to finely tune M protein mobility specifically at the PM. Collectively, our data highlighted the cornerstone membrane budding-priming activity of two spatially discrete M microdomains, potentially by coordinating the assembly of productive higher oligomers at the PM.IMPORTANCE Despite the availability of efficient vaccines, morbilliviruses (e.g., canine distemper virus [CDV] and measles virus [MeV]) still cause major health impairments. Although antivirals may support vaccination campaigns, approved inhibitors are to date still lacking. Targeting late stages of the viral life cycle (i.e., the cell exit system) represents a viable option to potentially counteract morbilliviral infections. The matrix (M) protein of morbillivirus is a major contributor to membrane budding activity and is assumed to assemble into dimers that further associate to form higher oligomers. Here, we rationally engineered M protein variants with modifications in two microdomains that potentially locate at dimer-dimer interfaces. Our results spotlight the cornerstone impact of both microdomains in membrane budding activity and further suggest a role of finely tuned high-order oligomer formation in regulating late stages of cell exit. Collectively, our findings highlight two microdomains in the morbilliviral M protein as novel attractive targets for drug design.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Center for Fish and Wildlife Health (FIWI)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gast, Matthieu Marc Alexandre, Kadzioch, Nicole Patrizia, Origgi, Francesco, Plattet, Philippe


500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture




American Society for Microbiology




Pamela Schumacher

Date Deposited:

09 Aug 2021 14:08

Last Modified:

05 Dec 2022 15:52

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

M-M interaction VLPs production dynamics at the cell surface matrix protein morbillivirus cell exit





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