Proteomic approaches to the study of papillomavirus-host interactions

Abstract

The identification of interactions between viral and host cellular proteins has provided major insights into papillomavirus research, and these interactions are especially relevant to the role of papillomaviruses in the cancers with which they are associated. Recent advances in mass spectrometry technology and data processing now allow the systematic identification of such interactions. This has led to an improved understanding of the different pathologies associated with the many papillomavirus types, and the diverse nature of these viruses is reflected in the spectrum of interactions with host proteins. Here we review a history of proteomic approaches, particularly as applied to the papillomaviruses, and summarize current techniques. Current proteomic studies on the papillomaviruses use yeast-two-hybrid or affinity purification-mass spectrometry approaches. We detail the advantages and disadvantages of each and describe current examples of papillomavirus proteomic studies, with a particular focus on the HPV E6 and E7 oncoproteins.

Figure 1

Sequence relatedness among HPV types. A phylogenetic tree based on the sequences of the L1 genes of the 143 human papillomavirus types currently listed in the Papillomavirus Episteme (PaVE) (van Doorslaer et al., 2012) was generated as described by (Dereeper et al., 2010; Dereeper et al., 2008). The HPVs are grouped into 5 genera (alpha, beta, gamma, mu, and nu), as shown. Genera are further subdivided into species, which are indicated (grey italics) for viruses in genus alpha and genus beta. Virus types discussed in the text are indicated in red.

Figure 2

Selected binding partners of HPV E7 proteins. HPV types used in the studies of Rozenblatt-Rosen et al and White et al on E7 interacting proteins (Rozenblatt-Rosen et al., 2012; White et al., 2012) were arranged into a phylogenetic tree based on the sequences of their L1 genes. Selected conserved, species-specific, or type-specific PPIs involving E7 proteins are indicated.

Figure 3

Selected binding partners of HPV E6 proteins. HPV types used in the studies of Rozenblatt-Rosen et al and White et al on E6 interacting proteins (Rozenblatt-Rosen et al., 2012; White et al., in press) were arranged into a phylogenetic tree based on the sequences of their L1 genes. Selected conserved, species-specific, or type-specific PPIs involving E6 proteins are indicated.