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Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Mutation S139N on Zika virus prM protein shifts immune response from Asian to contemporary strain
Jingzhe Shang1, Chao Zhou2, Mengjiao He2
1State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou 215123 Jiangsu, China; Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Beijing, China.
Abstract:
Zika virus (ZIKV) has been associated with neurological diseases like microcephaly and Guillain-Barré syndrome. The S139N single mutation on the prM protein of the FSS13025 Asian strain increases the mortality rate in mice. Therefore, it is a valuable tool for studying the impact of immune responses on neural damage. Here, we used single-cell sequencing technology to systematically assess the immune response induced by three ZIKV strains: Asian ancestral strain FSS13025/2010, FSS13025 strain with S139N mutation (FSS13025-S139N), and contemporary strain GZ01/2016. By infecting 1-day-old mice, we observed that the immune spectrum elicited by FSS13025-S139N mutant resembled that induced by the contemporary strain. The FSS13025-S139N strain induces the proliferation of inflammatory microglial cells earlier than the FSS13025 strain, similar to GZ01. A specific cell cluster, Microglia_Ccr7, was induced by the S139N mutant strain and GZ01 strain, which suppresses T cell activation through the PDCD1LG2-PDCD1 signaling pathway. Furthermore, the proliferation of CD8+ T cells was weakened and prolonged in S139N strain-infected samples. Finally, we found that the S139N mutant strain causes more apoptosis of neurons compared to the FSS13025 strain. These results indicate that the S139N mutation plays an important role in the immune response pattern of ZIKV and prolongs the duration of neuroinflammation.
Insights
The S139N mutation in Zika virus (ZIKV) prolongs neuroinflammation and increases neuronal apoptosis. This mutation alters immune responses, mimicking contemporary strains and impacting T cell activation.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Zika virus (ZIKV) is linked to severe neurological conditions, including microcephaly and Guillain-Barré syndrome.
- A specific mutation (S139N) in the FSS13025 Asian strain's prM protein elevates mortality in mice, making it a model for studying ZIKV-induced neural damage.
Purpose of the Study:
- To systematically analyze the immune responses triggered by three ZIKV strains: the ancestral FSS13025/2010, the FSS13025-S139N mutant, and the contemporary GZ01/2016.
- To elucidate the role of the S139N mutation in modulating ZIKV's impact on the immune system and neural tissue.
Main Methods:
- Single-cell sequencing technology was employed to assess immune responses.
- 1-day-old mice were infected with the three ZIKV strains to compare their effects.
Main Results:
- The immune response to the FSS13025-S139N mutant closely resembled that of the contemporary GZ01 strain.
- FSS13025-S139N induced earlier proliferation of inflammatory microglia and a specific Microglia_Ccr7 cluster, which suppresses T cell activation via the PDCD1LG2-PDCD1 pathway.
- CD8+ T cell proliferation was prolonged and weakened in mice infected with the S139N mutant, which also caused increased neuronal apoptosis compared to the FSS13025 strain.
Conclusions:
- The S139N mutation significantly influences ZIKV's immune response profile, leading to prolonged neuroinflammation.
- This mutation enhances ZIKV's neurovirulence, evidenced by increased neuronal apoptosis and altered immune cell dynamics.
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