Repository logo

Human cytomegalovirus deploys molecular mimicry to recruit VPS4A to sites of virus assembly.

Accepted version



Change log


Butt, Benjamin G 
Fischer, Daniela 
Rep, Alison R 
Schauflinger, Martin 
Read, Clarissa 


The AAA-type ATPase VPS4 is recruited by proteins of the endosomal sorting complex required for transport III (ESCRT-III) to catalyse membrane constriction and membrane fission. VPS4A accumulates at the cytoplasmic viral assembly complex (cVAC) of cells infected with human cytomegalovirus (HCMV), the site where nascent virus particles obtain their membrane envelope. Here we show that VPS4A is recruited to the cVAC via interaction with pUL71. Sequence analysis, deep-learning structure prediction, molecular dynamics and mutagenic analysis identify a short peptide motif in the C-terminal region of pUL71 that is necessary and sufficient for the interaction with VPS4A. This motif is predicted to bind the same groove of the N-terminal VPS4A Microtubule-Interacting and Trafficking (MIT) domain as the Type 2 MIT-Interacting Motif (MIM2) of cellular ESCRT-III components, and this viral MIM2-like motif (vMIM2) is conserved across β-herpesvirus pUL71 homologues. However, recruitment of VPS4A by pUL71 is dispensable for HCMV morphogenesis or replication and the function of the conserved vMIM2 during infection remains enigmatic. VPS4-recruitment via a vMIM2 represents a previously unknown mechanism of molecular mimicry in viruses, extending previous observations that herpesviruses encode proteins with structural and functional homology to cellular ESCRT-III components.



3101 Biochemistry and Cell Biology, 31 Biological Sciences, Infectious Diseases, 2 Aetiology, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Generic health relevance

Journal Title

PLoS Pathog

Conference Name

Journal ISSN


Volume Title


Public Library of Science (PLoS)
Wellcome Trust (098406/Z/12/B)
A Titan V graphics card used for this research was donated by the NVIDIA Corporation. BGB was a Wellcome Trust PhD student. This work was supported by a Sir Henry Dale Fellowship (098406/Z/12/B), jointly funded by the Wellcome Trust and the Royal Society (to SCG).