Protein-protein interactions of human viruses

Abstract

Viruses infect their human hosts by a series of interactions between viral and host proteins, indicating that detailed knowledge of such virus-host interaction interfaces are critical for our understanding of viral infection mechanisms, disease etiology and the development of new drugs. In this review, we primarily survey human host-virus interaction data that are available from public databases following the standardized PSI-MS format. Notably, available host-virus protein interaction information is strongly biased toward a small number of virus families including herpesviridae, papillomaviridae, orthomyxoviridae and retroviridae. While we explore the reliability and relevance of these protein interactions we also survey the current knowledge about viruses functional and topological targets. Furthermore, we assess emerging frontiers of host-virus protein interaction research, focusing on protein interaction interfaces of hosts that are infected by different viruses and viruses that infect multiple hosts. Finally, we cover the current status of research that investigates the relationships of virus-targeted host proteins to other comorbidities as well as the influence of host-virus protein interactions on human metabolism.

Keywords: Burden of disease; Interaction databases; Phage; Protein interaction network.

Fig. 1

Human proteins targeted by different virus families. The number of targets is based on all available interactions between viral and human host proteins, including 1,988 targets of Herpesviridae, 1,624 of Orthomyxoviridae, 1,740 of Papillomaviridae, 1,359 of Retroviridae and a pool of 3,301 targets of other virus families. Only a limited number of human proteins is targeted by many different virus families.

Fig. 2

Known human-virus interactions and sequenced viral genomes of virus families. In particular, the number of sequenced genomes of different virus families correlates with the number of known interactions between proteins of the family specific viruses and the human host (Spearman rank correlation coefficient r_SR = 0.41, P < 0.05). Furthermore, we labeled data points that correspond to virus families in Table 2, Table 4.

Fig. 3

The interactome-diseasome connection. Topological proximity between viral targets and genes associated with virally implicated diseases. Many diseases are directly or indirectly connected to virus proteins and their human targets. Modified after [72].