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

Martinez-Martin, Nadia

Interestingly, after the aforementioned haploid genetic screens identified NCP1 as a noncanonical entry receptor (given its intracellular localization), other filoviruses have been shown to take advantage of this receptor [135] . The relevance of this intriguing mechanism of viral entry is further reinforced by recent work on Lassa virus, an Old World Arenavirus that, similarly to Ebola virus, causes severe to fatal hemorrhagic disease in humans [48, 136] . A genome-wide haploid screen using VSV pseudotyped with Lassa glycoprotein was performed in order to identify host factors essential for viral entry. Although -dystroglycan (DAG1) was long recognized as the cell surface receptor for Lassa virus, additional factors were suspected, given the observation that certain DAG1-expressing cells are resistant to infection. The authors elegantly demonstrated that at a neutral pH, the Lassa virus glycoprotein was bound to DAG1, whereas upon exposure to lower pH (resembling the lysosome environment), a receptor switch occurred leading to strong association with the lysosomal-associated membrane protein 1 (LAMP1) [48] . Thus, similarly to Ebola virus, in the model suggested the virus would be incorporated into the endocytic pathway after interaction with its surface receptor DAG1, followed by increasingly acidic conditions that would result in interaction with LAMP1 in the lysosomal membrane, triggering membrane fusion and release of the virus in the cytosol [48] .