Elucidating the secretion proteome of human
Characterizing host-pathogen e PPI networks is therefore of utmost importance to gain a better understanding of the infection process and to inform the development of novel or improved therapeutic strategies.Excellent studies on mapping host-pathogen interactions, particularly MS-based analysis of viral infection, have provided a wealth of insight into infectious diseases [15–19].
In addition, more recently Kabanova and colleagues identified the cell surface receptor for the trimeric entry complex g Hg Lg O encoded by human cytomegalovirus (h CMV) .Thus, the elucidation of the e PPI networks on a global scale has become crucial for the biomedical research.However, in spite of their relevance and abundance, e PPIs are remarkably underrepresented in available large-scale datasets.Nevertheless, similarly to host e PPIs, a significant hurdle to the elucidation of host-pathogen biology has been the shortage of datasets of extracellular interactions between host and pathogen proteins, partly due to the technical challenges that these proteins present.Moreover, an additional consideration when studying pathogen-encoded molecules is that these proteins often lack any recognizable homology with any host molecules, thus precluding prediction of their functions [11, 20]. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pathogens have evolved unique mechanisms to breach the cell surface barrier and manipulate the host immune response to establish a productive infection.
Classical biochemical and biophysical approaches are particularly suitable for detection of high affinity host-pathogen interactions, such as those mediated by a viral capsid protein and a host cell surface receptor, or a pathogen-encoded glycoprotein and a secreted host factor.
Typically, these approaches have relied on the utilization of recombinant pathogen proteins as baits to probe for host binding partners, followed by immunoprecipitation and MS, or biophysical techniques for analysis of PPI such as surface plasmon resonance (SPR).
To allow host colonization, pathogens encode highly optimized protein modulators, in the form of secreted molecules or receptors expressed on the plasma membrane of the infected cells or the surface of the pathogen [11, 12].
Interactions between these proteins and extracellular host molecules form the foundation of communication between a host and a pathogen and play a vital role in the initiation and outcome of the infection [13, 14].
Several studies have shown that the g Hg Lg O trimer is involved in the infection of fibroblasts, whereas the g Hg LUL128L pentameric complex is required for entry into endothelial, epithelial, and myeloid cells [59–61].