Análise in silico do papel do receptor imune TREM-1 na infecção pelos Norovírus murino e humano
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2024-01-22
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Universidade Federal de Goiás
Resumo
In humans, Norovirus (NoV) is one of the main causes of acute diarrheal disease (ADD).
Due to the limitations of NoV cultivation, some molecular aspects of its interaction with
the host's immune system remain unknown. The triggering receptor expressed on myeloid
cells 1 (TREM-1) is associated with the amplification of inflammatory responses and the
progression of infections, including viral infections. Thus, we believe that TREM-1 may
be involved in the NoV infection. Initially, we investigated the expression of Trem1 and
the genes involved in its pathway, in transcriptomic data bank of public domain. In
experimental infection with murine Norovirus (MNoV), the expression of Trem1 was
increased. We also observed that there is a co-expression of Trem1 and genes involved in
the pyroptosis pathway, when compared to those in the apoptosis pathway. The in silico
protein-protein interactions were assessed by molecular docking simulations between the
Ig-like domain of murine TREM-1 and the P domain of the MNoV VP1 protein. The
murine TREM-1 recognized the conserved C´-D´ antigen that is present in the murine
VP1. In this regard, and based on phylogenetic criteria, different structures of the VP1
protein of NoV GII.4 strains from different years (1987, 2010, 2012, 2014, 2016 and
2019) were modeled. We performed docking and molecular dynamics (MD) simulations
to determine the in silico interaction between the VP1 protein of NoV GII.4 and the Iglike
domain of human TREM-1. The DM simulations suggest that there is a basic
interaction between human TREM-1 and the NoV VP1 protein, regardless of the year of
isolation. Interestingly, we observed changes in the participation of the different
complementarity determining regions (CDRs) of TREM-1 when interacting with the
domains of the VP1 protein, highlighting the participation of CDR3. Our data strongly
suggests the involvement of TREM-1 in the recognition of NoV and its participation in
the physiopathology of ADD caused by NoV.
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COLMENARES, Mike Telemaco Contreras. Análise in silico do papel do receptor imune TREM-1 na infecção pelos Norovírus murino e humano. 2024. 107 f. Dissertação (Mestrado em Biologia da Relação Parasito-Hospedeiro) - Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, 2024.