Volume 02 · Issue 03 · 2022

呼吸道病毒感染作为新发或再发传染病的主要原因，无疑是全球公共卫生的首要威胁。然而，在各种呼吸道病毒中，即腺病毒、流感病毒、鼻病毒、呼吸道合胞病毒以及冠状病毒，它们中的大多数引起症状轻微的自限性疾病。然而，少数可能发展为严重的发病率甚至死亡率。例如，α-冠状病毒HCoV-229E、HCoV-NL63和β-冠状病毒HCoV-OC43、HCoV-HKU1仅引起轻度普通感冒，而β-冠状病毒SARS-CoV、MERS-CoV和新型冠状病毒可导致致命感染，并通过全球大流行对人类公共健康构成巨大威胁。^[1]对于流感病毒存在类似的观察结果，如低致病性季节性流感（H3N2）与高致病性禽流感（H5N1和H7N9）和1918年大流行性流感（H1N1）。应紧急探索不同呼吸道病毒感染的潜在机制，以开发有效的干预方法。

病毒被认为是地球上最简单的生命形式，而人类是最复杂的，被我们自己奉承。尽管如此，病毒和人类免疫力之间的战争永无止境。一些人体器官，如呼吸道和肝脏，似乎是特定病毒的沃土，有时会导致侵袭性感染。免疫系统就像人类的军队，肩负着保卫身体的责任。军事行动是由一个复杂的系统进行的，这反映在其组成部分的复杂性上。专门的部队、物理环境、作战策略、精确的时机等构成了战争的生态系统。因此，即使是针对病毒的简单免疫应答也具有这些成分，因为数百万细胞动员到受感染的器官。一般来说，我们可能认为先天免疫是免疫系统的前进力量，而适应性免疫系统可以比作使用抗体和T细胞作为其主要力量的正规军。^[1]本专题致力于当前呼吸道和肝脏感染背景下免疫与病毒相互作用的科学前景，这可能为理解孙子在抗病毒免疫方面的兵法提供指导[图1].

为进一步做好新冠肺炎诊疗工作，我们组织专家对《新冠肺炎患者诊疗方案（暂定8^th版本），并开发了新冠肺炎患者诊疗方案（暂定9^th版本）.

During hepatitis B virus (HBV) infection, virus-infected hepatocytes directly cross-present viral antigens and regulate T cell response within the liver microenvironment. However, little is known regarding the regulatory pathways involved in viral antigen presentation in HBV-infected hepatocytes. This study investigated the underlying mechanism of antigen assembly and the HBV antigen-presenting function of major histocompatibility complex (MHC) class I molecules using heat shock protein gp96.

First, western blotting, flow cytometry, co-immunoprecipitation, GST pull-down, and confocal microscopic assays were performed to determine whether endogenous gp96 affects MHC-I levels via an antigen presentation pathway. Second, the B3Z assay and an AAV/HBV-infected hepatocyte-specific gp96-deficient mouse model were used to determine whether gp96 knockout functionally impaired peptide cross-presentation and produced a weakened antiviral cytotoxic T cell (CTL) response both in vivo and in vitro. Finally, confocal microscopic analysis and the B3Z assay were employed to show that exogenous gp96-associated peptide was present in MHC-I molecules via the endoplasmic reticulum (ER)-Golgi secretory pathway.

Compared with the control, gp96 knockdown significantly reduced the cell surface levels of MHC-I by approximately 75% (P < 0.01). Endogenous gp96 interacts with MHC-I and is involved in antigen presentation. Moreover, a weakened antiviral CTL response (34% compared to control mice) has been observed in hepatocyte-specific gp96-deficient mice following HBV infection. gp96 directed exogenous antigen to the ER, and the exogenous gp96-chaperoned peptide was endosome- and proteasome-dependent but not transporter associated with antigen processing dependent.

Cellular gp96 promotes the assembly and antigen presentation of MHC class I molecules. In addition, extracellular gp96 served as a natural adjuvant to induce a CTL response in a concerted and regulated manner within different cellular compartments. Our results elucidate the mechanism of assembly of MHC class I molecules by gp96, which may be beneficial for the design of immunotherapy and vaccines.

Many issues, such as severity assessment and antibody responses, remain to be answered eagerly for evaluation and understanding of COVID-19. Immune lesion is one of key pathogenesis of the disease. It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.

A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study. SARS-CoV-2 nucleocapsid (NP) antigen, specific IgM/IgG antibodies, and RNA were detected in sequential sera from three COVID-19 patients, and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay, colloidal gold quick diagnosis, and real-time RT-PCR, respectively. The clinical types of COVID-19 patients were classified into asymptomatic, mild, moderate, severe, and critical, following on the Chinese guideline of COVID-19 diagnosis and treatment. The demographic and clinical data of patients were obtained for comparable analysis.

NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms, and 60.13% (92/153) expanded samples collected within 17 days after illness onset. No SARS-CoV-2 RNA segment was detected in these sera. The NP positive proportion reached a peak (84.85%, 28/33) on 6 to 8 days after illness onset. Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19. Compared to NP negative patients, NP positive patients had older age [years, medians (interquartile ranges (IQR)), 49 (6) vs. 31 (11)], lower positive proportion of NP specific IgM [27.17% (25/92) vs. 59.02% (36/61)], and IgG [21.74% (20/92) vs. 59.02% (36/61)] antibodies, and longer duration [days, medians (IQR), 24 (10) vs. 21 (13)] from illness to recovery.

SARS-CoV-2 NP antigenemia occurred in COVID-19, and presented highly prevalent at early stage of the disease. The antigenemia was related to clinical severity of the disease, and may be responsible for the delay of detectable SARS-Cov-2 IgM.