ABSTRACT
COVID-19 pandemic, caused by infection Of severe acute respiratory syndrome Coronavirus 2 (SARS -CoV-2), is an ongoing and severe threat to public health and safety. The Coronavirus nucleoeapsid(N) protein mainly functions as a key structural protein, responsible for binding and packaging viral genome RNA into nucleocapsid and recruiting membrane(M) protein for virion assembly. In addition. the N protein functions as a regulatory protein and plays important roles in suppression of the host innate immune response, and localization with replication transcription complex (RTC) to facilitate Viral transcription and replication. Accumulating evidences have emerged recently that SARS-CoV-2 N protein undergoes liquid-liquid phase separation (LLPS) with RNA or other proteins. Importantly, phase separation of the N protein has been Shown to be essential for its structural and regulatory roles. Here, we summarize recent research progress on the phase separation of SARS-CoV-2 N protein. The potential of the phase separation of the N protein as a therapeutic drug targets is also discussed.
ABSTRACT
An unaddressed key question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T cell responses against SARS-CoV-2 in COVID-19 convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory CD4 and CD8 T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 and CD8 T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 and CD8 T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 T cells in the first 6-month post COVID-19 disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory CD4 and CD8 T cell responses were quite heterogenous between patients. Loss of memory CD4 T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.
Subject(s)
Memory Disorders , Severe Acute Respiratory Syndrome , T-Lymphocytopenia, Idiopathic CD4-Positive , COVID-19ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.