Science 20 years of dengue virus antigen evolution law

Written | Edited by Xueyue | Enzyme beauty antigen evolution occurs in a variety of viruses
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Changes in viral proteins recognized by the body's immune system can allow the virus to escape the immune response induced by previous similar virus infections
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Dengue virus (dengue virus DENV) consists of four different serotypes DENV1 to DENV4, which can interact with different antibodies in human serum
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DENV is transmitted by mosquitoes and infects about 400 million people each year, mainly in Southeast Asia and South America, and can cause mild and severe related symptoms
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High levels of cross-serotype reactive antibodies can prevent secondary DENV infections of different serotypes, while low to moderate levels of antibodies can increase the risk of dengue hemorrhagic fever or shock syndrome by antibody dependent enhancement (ADE)
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There are antigenic differences in DENV1-4, and no evidence of antigen escape has been found
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Each DENV serotype consists of 4-7 genotypes, and the difference in the amino acid level of the entire envelope protein is less than 10%
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The relationship between the evolution of DENV and the serotype of DENV has not been clarified
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Re-infection of the same serotype (homotypic) and different serotypes (heterotypic) of DENV has an unclear evolutionary and epidemiological impact
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The Derek AT Cummings team from the University of Florida published in Science titled Antigenic evolution of dengue viruses over 20 years.
The author systematically sequenced 384 strains of DENV in Thailand over the past 20 years for antigenic signature analysis.
The samples included virus envelopes and precursors.
Amino acid variation in membrane protein
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In order to expand to global sample types, the author also analyzed the antigenic characteristics of 64 DENV strains isolated from 1944 to 2012 in 20 different countries
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The author measured the PRNT50 of 412 strains of DENV
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The PRNT titer is lower than that associated with an increased risk of severe dengue fever
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All viruses were titrated with the antiviral serum of 20 African green monkeys inoculated with different DENV viruses
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Next, the author uses the antigen mapping method to evaluate the antigenic relationship between virus strains
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The results show that DENV has antigenic diversity.
The antigenicity of virus strains from Thailand is closer, and the antigenicity of virus strains from Asia, Oceania or America and other countries in Africa is more different
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DENV4 genotypes I and III are mainly prevalent in Thailand.
Compared with DENV4 genotype II which is prevalent in America and Africa, they have stronger antigenicity
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The level of antigenicity of DENV genotype II is comparable to that of other serotypes
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The author used antigen kinetics to quantitatively determine the antigen distance to verify the existence of antigen diversity
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By measuring the antigenic distance, the author verified the previous hypothesis: the previously circulating virus strains will choose different antigenic virus strains to avoid the immune system attack after being baptized by the body's immune system
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A high cross-serum reaction can be induced several months after primary DENV infection or several years after secondary infection
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After the pandemic of other serotypes, DENV will choose a serotype that can evade immune attack
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The author also observed that serotypes periodically evolve into similar antigen types
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There is also a hypothesis that cross-serotype antibodies will weaken the ADE effect after the initial infection, thereby "pulling" the serotype to other types
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On average, with the increase in the incidence, the level of antigenic similarity between the serotype and the early virus strains of the same year is lower, which shows that there is a close relationship between the changes in population antigen levels and the annual DENV epidemiology
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2D map of DENV1-4 antigen isolated from Thailand This article uses 412 virus strains and decades of DENV epidemic characteristics to discover the evolutionary laws of antigens within the genotype.
The purpose of evolution is mainly to avoid isotype protection
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However, the author also pointed out that the samples are still limited, and most of them are collected from pediatric hospitalized cases, which may not reflect the complete epidemic and evolutionary characteristics
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This work still constitutes the most comprehensive DENV data set so far, analyzes a more comprehensive evolutionary law of virus antigens, and provides valuable information for virus detection and vaccine evaluation
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Pejman Rohani and John M.
Drake from the University of Georgia commented on this article at the same time
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They pointed out that there are two very promising research areas in the future: one is to combine multiple technologies to explore the mechanism that determines the structural changes of the virus envelope protein; the other is to build a multi-scale system dynamics model and transmission dynamics of virus evolution, which is useful for analyzing the epidemic and The causal relationship between antigenic evolution is crucial
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Dengue vaccine Dengvaxia has been approved for 6 years, and studying the evolution of DENV is also very important to understand when to use neoantigen vaccines
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Therefore, a comprehensive understanding of antigenic evolution is of great benefit to public health
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Link to the original text: http://doi.
org/10.
1126/science.
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