TREM-1 as a Potential Coreceptor in Norovirus Pathogenesis: Insights from Transcriptomic Analysis and Molecular...

Norovirus (NoV) is a major cause of acute diarrheal disease in humans. However, due to complications in cultivating this virus, bioinformatics aids in elucidating the virus-host relationship. One of the molecules that has been associated with the burden of viral diseases is TREM-1, mainly due to its role in amplifying the inflammatory response. Thus, we hypothesized that TREM-1 may be involved in NoV infection. Analysis of public transcriptomic data sets showed an increased expression of Trem1 and Trem3 during murine NoV (MNoV) infection. Then, molecular docking was performed between murine TREM-1 and the P domain of the MNoV VP1 protein. The viral antigenic segment C'-D' was recognized by the murine TREM-1 CDR1 region. Subsequently, based on phylogenetic criteria, NoV VP1 proteins from the GII.4 genotype sequenced in different years (1987, 2010, 2012, 2014, 2016, and 2019) were modeled. Using docking and molecular dynamics simulations, a stable interaction was observed between the human TREM-1 Ig-like domain and the conserved S and P segments of the NoV VP1 protein. Notably, this interaction was conserved over the years and was mainly dictated by the TREM-1 CDR3 region. Also, coexpression between Trem1 with genes involved in apoptosis and pyroptosis pathways was surveyed during viral infection by MNoV. It was found that Trem1 is primarily expressed with genes from the pyroptosis pathway. These simulations strongly suggest the involvement of TREM-1 in NoV pathogenesis and its potential contribution as a coreceptor.