Science: Reveals protein NRLP1 specific identification of double-stranded RNA to detect viral infection mechanisms

Nov 29, 2020 /--- In a new study, Veit Hornung of the University of Munich in Germany and his team confirmed that a protein found in skin cells called NRLP1 identifies specific nucleic acid intermediates formed during virus replication.
this recognition process then induces a powerful inflammatory response.
results were published online November 26, 2020 in the journal Science under the title "Human NLRP1 is a sensor for double-stranded RNA."
photo from Journal of Virology, 2015, doi:10.1128/JVI.03645-14.
ability to distinguish between the self and potentially harmful non-self is essential for the integrity and survival of the organism.
in most organisms, the so-called innate immune system is responsible for identifying such intruders (non-self).
proteins that perform this task are a class of proteins called inflammasome sensors.
activated, these sensing proteins form inflammatory complexes and trigger a series of inflammatory reactions that in some cases can lead to the death of infected cells.
In the new study, Hornung's team, in collaboration with colleagues at the Technical University of Munich and the Max Planck Institute for Biochemistry, has now confirmed that one such sensor protein found in skin cells binds directly to specific molecular structures produced during the replication of certain RNA viruses.
new findings underscore the importance of corted cells as a barrier against invading pathogens.
the NRL P1 protein was the first inflammatory body sensing protein to be found and characterted.
, "So far, it remains unclear whether NLRP1 really works as a direct sensing protein for non-self-molecules," Hornung said.
humans, NLRP1 is found mainly in cells called cells, which form the outer layer of the skin and act as a physical barrier against bacteria and viruses.
in this study, the researchers first tested the cells' response to viruses with different replication mechanisms and identified a virus called Semliki Forest Virus (SFV), which strongly activates NLRP1.
"Other cells known to have barrier functions, such as bronchal endocys, also respond to the virus by activating NLRP1, so this seems to be a common phenomenon," said Stefan Bauernfried, the first author of the paper.
" SFV virus was first discovered in Uganda and used as a useful experimental model in virology.
it is mainly found in rodents, although it can also be transmitted to humans by mosquitoes.
SFV is a single-stranded RNA virus in which its genetic material consisting of single-stranded RNA is packaged in the virus's enclosure.
, however, the process of virus replication requires the synthesis of a complementary chain that is paired with the parent chain to produce double-stranded RNA.
the formation of double-stranded RNA as a replication intermediate is a feature of many viruses.
, however, do not usually appear in the cells of higher organisms, making them good candidates for innocular immune system recognition.
, bio-chemical experiments have shown that NRLP1 is specifically able to bind double-stranded RNA.
this type of sensing protein is difficult to study because they tend to form aggregates, " explains Bauernfried, a researcher at the University of New China.
this, we were able to purify the NLRP1 construct, and we went on to confirm that it binds directly to double-stranded RNA and is activated by double-stranded RNA.
" summary, these findings suggest that NLRP1 is a key factor in identifying viral infections in barrier tissues such as skin.
be particularly important for detecting viruses that do not optimally adapt to potential hosts.
not know whether and to what extent it was also involved in testing other viruses that are pathogenic to humans.
hornung, "it is not entirely impossible for well-adapted viruses to gain the ability to suppress this particular response mechanism."
's an issue we're going to explore in future studies, " he said.
" (Bioon.com) Reference: 1. Stefan Bauernfried et al. Human NLRP1 is a sensor for double-stranded RNA. Science, 2020, doi:10.1126/science.abd0811.2.How epithelial cells ward off viruses。