# TREM-1 Interacts with Rotavirus Proteins and Drives Inflammatory Responses: A Combined Experimental and Computational Approach

## TL;DR

This study shows that TREM-1, an immune receptor, interacts with rotavirus proteins and enhances inflammation during infection.

## Contribution

The study identifies TREM-1 as a novel mediator in rotavirus infection and host-virus interactions.

## Key findings

- TREM-1 and its associated genes are upregulated in rotavirus-infected mice and children.
- Inhibiting TREM-1 reduces IL-1β production and cytopathic effects in rotavirus-infected cells.
- TREM-1 interacts with rotavirus proteins VP5* and NSP4, suggesting roles in viral attachment and immune stimulation.

## Abstract

Rotavirus (RV) is one of the main etiologic agents associated with diarrheal diseases (DDs), being responsible for approximately 200 thousand deaths annually. Currently, there are still many aspects regarding the virus biology, cell cycle, and pathophysiology of RV that need further elucidation. Therefore, the present work aimed to investigate whether the triggering receptor expressed on myeloid cells 1 (TREM-1) might be associated with RV infection. This immune receptor has been observed as an amplifier of inflammatory responses in different infectious and non-infectious diseases, including inflammatory bowel disease and celiac disease. Initially, we searched for public transcriptomic data regarding RV infection and the expression of TREM-1 and its associated genes, which were significantly upregulated in infected mice and children. Then, we infected monocytes with the virus, with or without a TREM-1 inhibitor. The inhibition of the receptor’s activity resulted in a significant decrease in IL-1β production. We also observed a reduction in cytopathic effects when MA104 cells were treated with TREM-1 inhibitors and then infected with simian RV. To further elucidate the interactions between the virus and TREM-1, in silico tools were used to simulate interactions between the receptor and RV proteins. These simulations suggested the occurrence of interactions between TREM-1 and VP5*, a protein involved in viral attachment to target cells, and also between the receptor and NSP4, a viral enterotoxin with immunostimulant properties. Hence, our results indicate that TREM-1 is involved in RV infection, both as a mediator of inflammatory responses and as a player in the host–virus relationship.