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The novel coronavirus is still rampant, and the number of confirmed cases is still rising by a large margin every day. This time, the new coronavirus pneumonia is overwhelming. Since 2003, we have experienced the terrifying SARS outbreak, namely the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). In 2012, the Middle East Respiratory Syndrome Coronavirus (MERS CoV) with a mortality rate of 36% broke out in Saudi Arabia. In just nearly 20 years, humans have experienced three explosive outbreaks of the coronavirus, which deeply demonstrates the enormous threat this virus family poses to humanity.
Whether it's novel coronavirus, flu, or common ailments, or no symptoms, our immune system is always active in the front line. As stated in the "Quick Guide for Diagnosis and Treatment of novel coronavirus Pneumonia" formulated by the expert group of Tongji Hospital, "people generally lack immunity to this virus and are susceptible to it. If they are exposed to a large number of viruses or patients with poor immune function, they are very likely to be infected." Who is susceptible to viruses, influenza and other diseases, and who is not? How is the susceptibility to viruses, influenza and other diseases determined? Many experts and scholars have different focuses, and some teachers have made efforts to explore the HLA field:
01 HLA gene polymorphism and susceptibility to coronavirus and influenza
Chen Zhenfeng; Wei Maoti; Hu Jielan; Zhang Keju; He Li; Han Yi; Huiwuli; Wang Shixin;; A study on the relationship between HLA-B gene polymorphism and susceptibility to severe acute respiratory syndrome coronavirus [J]; Chinese Journal of Preventive Medicine; Issue 01, 2010
The susceptibility relationship of some loci in gene polymorphism has always been a hot research topic for SARAS virus. Researchers from the Medical College of the Chinese People's Armed Police Force analyzed the relationship between HLA-B gene polymorphism and susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV) to reveal the role of genetic factors in the onset of severe acute respiratory syndrome (SARS). Method: A case-control study design was adopted, and the PCR-SBT method was used to study the distribution of HLA-B alleles in 43 SARS recovered patients, 30 high-risk medical staff controls, and 62 healthy controls. Serotypes were designated based on genotype for analysis. The results showed that HLA-B * 51G1 (including B * 510101, B * 510105, B * 510107, B * 5111N, B * 5130, and B * 5132 genotypes) and 5502 genotypes may play a protective role in the occurrence of SARS, and HLA-B * 130201 and 5801 genotypes may be susceptible factors for SARS. According to serum typing, B13 and B35 are susceptible factors for SARS-CoV infection, while B07, B27, and B49 are protective factors for SARS-CoV infection.
Liu Xueting, Wang Shan, Zhang Junyan, etc Prediction of antigenic epitopes of HA and NA proteins of H7N9 influenza virus and analysis of their correlation with HLA class II alleles [D], two thousand and fifteen
The research team of the Allergy Research Office of the State Key Laboratory of Respiratory Diseases analyzed the homology of HA and NA, B cell epitopes, T cell epitopes, and HLA class II alleles with strong binding power with HA and NA through software. Because the HLA allele DRB1 * 0701 has strong binding power with HA and NA, and the gene frequency is high in people in Xinjiang, Harbin, Shandong, Liaoning, Beijing, Shijiazhuang, Tianjin and other northern regions of China, the team believes that HLA-DRB1 * 0701 is highly related to H7N9 influenza virus, and H7N9 influenza virus is in Xinjiang, Harbin, Shandong, Liaoning, and Beijing Shijiazhuang and Tianjin are easier to spread.
02 HLA-A2 accelerates the synthesis of peptide vaccines for viruses, influenza, and other diseases
Cellular immunity plays a crucial role in anti-tumor and antiviral immunity. HLA-A2 is a highly distributed MHC class I molecule in the population, with a positivity rate of up to 40% in the Chinese population, ranking first in the MHC-I subgroup. Therefore, it is the preferred molecule for vaccine research. With the deepening understanding of the interaction between MHC class I molecules and epitope molecules, scientists have established a relatively mature epitope identification technology route. The main steps are as follows: ① Based on the characteristics of the interaction between epitopes and MHC class I molecules, predict the restricted CTL epitopes of MHC class I molecules, and use computer molecular simulation technology to further screen the predicted epitopes; ② Determine the binding affinity between epitopes and MHCI class molecules: ③ Use in vitro cytotoxicity analysis or immune tumor bearing transgenic mice to identify whether skin epitopes can induce CTL and seek the optimal dominant epitope. Based on this technical route, multiple HLA-A2 restrictive CTL epitopes have been identified.
Wang Qing, Zhou Furong, Wu Yuzhang Prediction of HLA-A ^ * 0201 Restrictive CTL Epitope of SARS Coronavirus N Protein [D], two thousand and four
The Institute of Immunology at the Third Military Medical University predicted the HLA-A * 0201 restrictive CTL epitope of the SARS coronavirus N protein. By combining artificial neural networks and quantitative matrices, HLA-A * 0201 binding peptides were predicted and CTL epitopes were screened. Six nine peptide CTL epitopes were predicted, providing basic data for understanding the immune protection and immunopathological mechanisms of SARS coronavirus and vaccine development
PoorinMohammad N, Mohabatkar H. Identification of HLA-A * 0201-restricted CTL episodes from the receiver binding domain of MERS CoV spike protein using a combinatorial in silicon approach [J] Turkish Journal of Biology, 2014, 38 (5): 628-632
In 2012, the Middle East Respiratory Syndrome Coronavirus (MERS CoV) received attention due to its high mortality rate and pandemic potential. PoorinMohammad and his team aim to develop peptide based vaccines against MERS by analyzing the cytotoxic T lymphocyte epitopes of the most common class I HLA allele HLA-A * 0201 in the Middle East population, observing their interaction characteristics with major histocompatibility complex (MHC) molecules, as well as the binding behavior of MHC epitope complexes with human T cell receptors. By selecting the predicted epitope with the best binding characteristics for the development of MERS vaccines, epitope based vaccine design can effectively minimize the huge experimental workload and accelerate the speed of peptide vaccine development.
Wang Feipeng Prediction and comparative study of HLA-A~* 0201 restricted CTL antigen epitopes of influenza A H1N1 virus [D] Jinan University, 2011
In addition to the coronavirus, influenza has also been causing frequent disturbances to animals and humans in recent years. Jinan University predicts the HLA-A * 0201 restricted cytotoxic T lymphocyte (CTL) antigenic epitopes of three influenza viruses, namely influenza A H1N1, avian influenza H5N1, and human influenza H3N2. The CTL antigenic epitope prediction software SYFPEITHI is used to predict the HLA-A * 0201 restricted CTL antigenic epitopes of proteins encoded by influenza virus genes such as influenza A H1N1, and to compare and analyze the predicted CTL antigenic epitopes. It has been proven that there is antigen cross reactivity among three influenza viruses, and CTL targeting these antigen epitopes can simultaneously recognize cells infected by the three viruses, providing experimental data for the research and application of influenza vaccines.
According to the above paper, the study of HLA gene polymorphism plays a crucial role in SARS, MERS, and influenza. Considering the high genetic similarity between 2019 nCoV and SARS-CoV, existing immunological studies on SARS-CoV and MERS CoV can further explore vaccine design for 2019 nCoV. At the same time, it is also possible to use the polymorphism of HLA genes in the concentrated sample typing for this new type of pneumonia to study population coverage of high susceptibility genes. It is even possible to carry out antigen genotyping of immune cells for the diagnosed asymptomatic patients with COVID-19 this time, and use big data to integrate the susceptibility genes of high-risk population for 2019 nCoV, the genotype of asymptomatic patients, the possible protective gene sites of rehabilitation patients and other specific points. I believe that this series of big data can provide a broad reference for the world and also help guide experimental work on developing targeted 2019 nCoV vaccines. Thus, we will not panic and cause heavy losses in the face of the next novel coronavirus, or any new virus. After all, long-term and stable preparedness can calmly cope. Weihe, who has been committed to HLA typing services for many years, is also willing to seek guidance in the follow-up research work of 2019 nCoV, providing accurate HLA gene typing related technical services and test kits, conducting HLA typing tests on a large number of case samples, and working together to resist the coronavirus.
Wuhan, come on! Hubei, come on! Go China!
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