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Published on: March 1, 2019
Immune evasion, infectivity, and membrane fusion of the SARS-CoV-2 JN.1 variant
Haijun Tang1,2, Yanhang Zhuo1,2, Jianlin Chen1,3
1Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Abstract:
SARS-CoV-2 undergoes continuous mutations during transmission, resulting in a variety of Omicron subvariants. Currently, SARS-CoV-2 BA.2.86 and its descendants JN.1, KP.2, KP.1.1 have been identified as the primary variants spreading globally. These emerging Omicron variants have increased transmissibility, potentially elevating the risk of viral reinfection in the population. However, the biological characteristics of newly-emerged Omicron subvariants in infecting host cells remain unclear. In this study, we assessed the neutralization effect of BA.2.86 and its descendant JN.1, as well as D614G, BA.2, BA.4/5, XBB.1.5, EG.5.1, HV.1, HK.3, JD.1.1 and JG.3 on convalescent sera obtained from individuals infected with BA.5 or XBB.1.5 strain. We evaluated the biological characteristics of variants spike proteins by measuring viral infectivity, affinity for receptors, and membrane fusion. Compared to XBB-related subvariants, BA.2.86 exhibited a diminished immune escape response, but JN.1 displayed a markedly augmented immune escape capability, which was closely related to its rapid transmission. BA.2.86 was less infectious in susceptible cells, while the JN.1 variant exhibited relatively high infectivity. Notably, BA.2.86 and JN.1 exhibited low fusion activity in 293 T-ACE2 cells, but relatively high fusogenicity in transmembrane protease serine 2 (TMPRSS2) overexpression cells. This study explored the evolutionary characteristics of emerging Omicron subvariants in host adaptation, and provided new strategies for the prevention and treatment of coronavirus disease 2019 (COVID-19).
Insights
The SARS-CoV-2 Omicron subvariants BA.2.86 and JN.1 show distinct characteristics. JN.1 exhibits increased immune escape and infectivity, contributing to its rapid global spread and potential for reinfection.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) continuously mutates, leading to new Omicron subvariants like BA.2.86 and its descendants (JN.1, KP.2, KP.1.1).
- These variants display increased transmissibility, raising concerns about viral reinfection.
- The biological mechanisms of newly emerged Omicron subvariants in host cell infection are not fully understood.
Purpose of the Study:
- To assess the neutralization effects of convalescent sera against various SARS-CoV-2 Omicron subvariants, including BA.2.86 and JN.1.
- To evaluate the biological characteristics of these variants, focusing on viral infectivity, receptor affinity, and membrane fusion.
- To explore the evolutionary traits of emerging Omicron subvariants concerning host adaptation.
Main Methods:
- Neutralization assays using convalescent sera from individuals infected with BA.5 or XBB.1.5.
- Evaluation of viral infectivity in susceptible cells.
- Measurement of spike protein affinity for receptors and membrane fusion activity in 293T-ACE2 and TMPRSS2-overexpressing cells.
Main Results:
- BA.2.86 showed diminished immune escape compared to XBB-related subvariants, while JN.1 demonstrated significantly augmented immune escape.
- JN.1 exhibited higher infectivity in susceptible cells than BA.2.86.
- Both BA.2.86 and JN.1 displayed low fusion activity in 293T-ACE2 cells but higher fusogenicity in TMPRSS2-overexpressing cells.
Conclusions:
- JN.1's enhanced immune escape and infectivity correlate with its rapid transmission.
- BA.2.86 and JN.1 possess distinct evolutionary characteristics influencing host cell entry and adaptation.
- Findings offer insights for developing new strategies for COVID-19 prevention and treatment.
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