Volume 36, Issue 3, March 2011, Pages 159169

Review

How viruses hijack cell regulation

Norman E. Davey1, Gilles Trav2, Toby J. Gibson1
1

Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany Equipe Oncoproteines, FRE CNRS 3211, ESBS, 1, Bld Sbastien Brandt, BP10413, 67412 Illkirch, France

Choose an option to locate/access this article: Check if you have access through your login credentials or your institution Check access Purchase $35.95

Viruses, as obligate intracellular parasites, are the pathogens that have the most intimate relationship with their host, and as such, their genomes have been shaped directly by interactions with the host proteome. Every step of the viral life cycle, from entry to budding, is orchestrated through interactions with cellular proteins. Accordingly, viruses will hijack and manipulate these proteins utilising any achievable mechanism. Yet, the extensive interactions of viral proteomes has yielded a conundrum: how do viruses commandeer so many diverse pathways and processes, given the obvious spatial constraints imposed by their compact genomes? One important approach is slowly being revealed, the extensive mimicry of host protein short linear motifs (SLiMs).

Figures and tables from this article:

Figure 1. A representative selection of motif-rich viral proteins, and an illustration of the diverse range of functions hijacked by experimentally validated examples of viral motif mimicry. (a) Prototypic motif-rich viral proteins LMP1 [34], Nef [101] and E1A [43] with illustrative tertiary structure. Many of the motifs form a secondary structure when bound, yet, with the exception of the central core of Nef, the proteins are largely devoid of globularity in their native state. Each protein uses motifs for a different function (see colour scheme in panel (b)). The majority of motifs in LMP1 rewire cell signalling, the motifs of Nef mediate targeting and localisation, and those of E1A regulate transcriptional and epigenetic activities. (b)SLiMs roughly classified by function. The numbering scheme corresponds to the examples provided in Table 1. Figure options

Figure 2. Simplified schema representing examples of viral mimicry of host SLiMs. Viruses mimic host motifs to hijack numerous cellular pathways, thus subverting a diverse range of distinct functions (Figure 1b). (a) HIV Vpu promotes CD4 degradation. (b) EBV LMP1, a constitutively active CD40 mimic, induces NF-B activation. (c) HSV 134.5 reverses protein synthesis shutdown through recruitment of PP1 to phosphorylated eIF2. (d) Adenovirus E1A activates E2F-controlled transcription by mediating dissociation of E2F from RB. (e) HIV Rev contains a molecular switch, comprising an NLS and an RRE-binding motif, to control RNA shuttling. Figure options

Figure 3. Solved structures of viral motifs in complex with their host targets. Motifs are shown as orange ribbons, and host binding partners as grey ribbon diagrams. The numbering scheme corresponds to Table 1, with a functional colouring scheme: red: viral egress; purple: protein degradation; brown: cell cycle; green: cell signalling; light green: transport; pink: transcriptional regulation; grey: epigenetic regulation. Labels are in the format: Virus viral protein motif host binding partner. Figure options

Table 1. Representative examplesa of viral mimicry of host SLiMs

View Within Article

Copyright 2010 Elsevier Ltd. All rights reserved