Technologies for Proteome-Wide Discovery of Extracellular Host-Pathogen Interactions

Martinez-Martin, Nadia

Alongside protein microarrays-based technologies, MS, and computational analysis, the explosion of the functional genomics field in the last years has revolved the avenues to study pathogen interactions with their hosts, often in high throughput. In brief, genetic screens comprise gain-of-function and loss-of-function strategies, represented by complementary DNA (cDNA) libraries and RNA-interference-(RNAi-) based approaches, respectively. These methods were developed more than two decades ago and have been widely utilized by the scientific community, providing fundamental insights into the infection process. In particular, the cDNA libraries have proven extremely successful in identifying viral receptors through a gainof-function approach, upon transduction of the cDNA library from a susceptible cell line into nonpermissive cell lines. The use of cDNA libraries is not reviewed in detail here in the interest of a more comprehensive revision of relative newer genomics-based approaches, such as the clustered regularly interspaced short palindromic repeat/ CRISPR-associated protein 9 (CRISPR/Cas9) or the haploid cell screens. Nevertheless, these libraries have represented one of the most significant technologies to further our understanding of the pathogen-host interaction. For example, early studies made use of cDNA libraries to shed light on the complex mechanism exploited by hepatitis C virus for initial invasion of the cell [37] [38] [39] , identified CAR as a common receptor for adenovirus 5 and coxsackievirus B [40] , and were instrumental to identify SLAM1 and PVR as a receptors for measles and poliovirus, respectively [119, 120] .