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In July 2022, Zhou Xi's team from Wuhan Institute of Virology/State Key Laboratory of Virology, Chinese Academy of Sciences published a paper entitled "Dual Inhibition of Innate Immunity and Apoptosis by Human Cytomegalovirus Protein UL37x1 Enables Efficient Virus Replication" in the international authoritative academic journal Nature Microbiology research paper
.
This study revealed a new mechanism by which human cytomegalovirus (HCMV), through its encoded UL37x1 protein, inhibits the dual inhibition of antiviral innate immunity and apoptosis, which is of great significance for revealing the interaction between HCMV and host immunity and the pathogenic mechanism
.
.
This study revealed a new mechanism by which human cytomegalovirus (HCMV), through its encoded UL37x1 protein, inhibits the dual inhibition of antiviral innate immunity and apoptosis, which is of great significance for revealing the interaction between HCMV and host immunity and the pathogenic mechanism
.
Viral infection will stimulate the host cell's antiviral innate immune response, and the virus will also encode some proteins or factors that antagonize innate immunity, thereby achieving immune escape
.
In addition, apoptosis is also an important antiviral mechanism, and many viruses have also been found to encode proteins with apoptosis inhibitory function
.
However, a large number of studies have also shown that apoptosis can inhibit innate immune signaling pathways
.
So, do viral proteins with apoptosis-suppressing functions lead to up-regulation of innate immune responses, and does this "up-regulation" create a microenvironment that is "unfavorable" for viruses in cells? How does the virus respond to this challenge and strike a balance between antagonizing apoptosis and escaping immunity?
.
In addition, apoptosis is also an important antiviral mechanism, and many viruses have also been found to encode proteins with apoptosis inhibitory function
.
However, a large number of studies have also shown that apoptosis can inhibit innate immune signaling pathways
.
So, do viral proteins with apoptosis-suppressing functions lead to up-regulation of innate immune responses, and does this "up-regulation" create a microenvironment that is "unfavorable" for viruses in cells? How does the virus respond to this challenge and strike a balance between antagonizing apoptosis and escaping immunity?
In response to this important scientific question, the team used HCMV-infected cells and humanized mice as models and found that the UL37x1 protein encoded by HCMV not only has the function of suppressing apoptosis, but also antagonizes innate immunity by directly binding to the host TBK1 protein
.
More interestingly, its inhibitory effect on innate immunity completely counteracted the upregulation of immunity caused by its inhibition of apoptosis, ultimately enabling HCMV to replicate more efficiently
.
This study revealed the molecular mechanism by which HCMV achieves a "balance" between inhibiting apoptosis and antagonizing innate immunity, providing a new way to better understand the replication and activation mechanism of HCMV, and to further study and improve the virus-host interaction mechanism.
direction and ideas
.
.
More interestingly, its inhibitory effect on innate immunity completely counteracted the upregulation of immunity caused by its inhibition of apoptosis, ultimately enabling HCMV to replicate more efficiently
.
This study revealed the molecular mechanism by which HCMV achieves a "balance" between inhibiting apoptosis and antagonizing innate immunity, providing a new way to better understand the replication and activation mechanism of HCMV, and to further study and improve the virus-host interaction mechanism.
direction and ideas
.
Associate Researcher Ren Yujie of Wuhan Institute of Virology is the first author of the paper, Researcher Zhou Xi and Qiu Yang Youth Researcher of Wuhan Institute of Virology, and Professor Zhou Wei of Guangzhou Women and Children's Medical Center are the co-corresponding authors of the paper
.
The research was supported by the National Natural Science Foundation of China, the Strategic Pilot B of the Chinese Academy of Sciences, and the Youth Innovation Promotion Association of the Chinese Academy of Sciences
.
.
The research was supported by the National Natural Science Foundation of China, the Strategic Pilot B of the Chinese Academy of Sciences, and the Youth Innovation Promotion Association of the Chinese Academy of Sciences
.
Article link:
Figure 1.
Dual inhibitory mechanism of HCMV UL37x1 on apoptosis and immunity
Dual inhibitory mechanism of HCMV UL37x1 on apoptosis and immunity
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