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Can viral macrogenomics approaches detect emerging viruses that are still in latency?

It can be found. The application of some of the earlier traditional research methods is limited and does not fully meet the needs of virus research. Such as electron microscopy to observe the sensitivity of the virus is not high, cell culture virus may not be observed cell lesions, serological reaction is not only difficult to obtain high-value antibodies and easy to cross-react to lead to erroneous results, the traditional PCR method of unknown sequences and high variability of the virus research is difficult to play a role. In addition, the frequent occurrence of viral epidemics and their terrible infectiousness in recent years have posed a serious threat to the health of human beings, animals and plants, such as HIV virus, SARS virus, avian influenza virus and the Ebola virus that raged in West Africa and other places [4], which have caused great panic and economic losses to the people. Therefore, the study of viral genomes, the exploration of pathogenic sources, how viruses exist and spread in organisms and environments, and the study of viral disease prevention and control have become urgent.

With the development of the times and the progress of biological science and technology, the emerging viral macrogenomics provides an opportunity to solve these problems.The concept of macrogenomics (Metagenomics) was first proposed by Handelsman [5] in 1998 to study the sum of genomes in a specific environment, including cultured and uncultured microorganisms. Viral metagenomics (VMG) is the application of macrogenomics in the field of viruses, i.e., the technique of analyzing biological information by concentrating the genetic material of viral particles from the environment or biological tissues. Its application requires the support of some cross-disciplinary innovative technologies. The application of random primer PCR and next-generation sequencing technology---high-throughput sequencing greatly improves the efficiency of the research and the abundance of the information obtained, overcomes the shortcomings of low concentration of viruses in the general environment and easy to be interfered with, and expands the scope of application and practical role of viral macro-genomics, providing broad prospects and application space for the exploration of unknown viruses. It has significant contributions in human disease prevention and vaccine development.

Traditional methods can only target known viruses, and it is difficult to discover new viruses, while viral macro-genomics method combines next-generation sequencing technology and stochastic PCR1 viruses; the viruses studied are obtained directly from the environment, without the need for isolation and cultivation; and viruses that are too dispersed in the environment and low in abundance can be systematically analyzed and identified.

Limitations

The application of viral macro-genomics methods for research still has some problems that need to be further explored, such as the way of extracting samples from a large number of environments, whether the selection of random amplification methods and primers can be done to cover all the viruses without any bias, the processing of massive sequencing data, and the bioinformatic analysis that relies on the complexity of the samples.

3.1 Clinical applications

In 2008 [16] viral macro-genomics was used for the first time in the clinical examination of human beings, in combination with deep sequencing to detect pathogens of lethal diseases associated with organ transplantation. Detection and analysis of human saliva, respiratory tract, blood, and excreta using viral macrogenomics can detect unknown and potentially pathogenic viruses.

Law et al. studied plasma from a number of patients with liver disease and found that the viral macrogenomics approach was rapid and accurate, and also extended detection to other body fluids.

Tong-Ling Shan analyzed enterovirus communities in children and pigs based on a viral macrogenomics approach and identified information on the causative agent.

Zhang et al. applied macrogenomics to identify a large number of plant viruses in human feces.

Willner et al. applied macrogenomics to analyze DNA virus communities in respiratory secretions from healthy and respiratory-infected humans.

Viral macrogenomics was applied in 2010 to obtain the entire genes of influenza viruses without a priori information. Researchers have also monitored viruses carried by insect vectors known to transmit human, animal and plant viruses in specific regions [22],to detect the prevalence and prevention of associated viruses and to provide direction for the identification of outbreak pathogens. As bats serve as natural hosts for the transmission of many human-animal ****diseases (e.g., Ebola virus, Severe Acute Respiratory Syndrome (SARS) virus, and Nipah virus), the diversity of viruses in bats has become a hotspot for scholars to study.

In 2010, Li et al. and Donaldson et al. applied a viral macrogenomics approach to study the viral communities in the feces of North American bats, respectively. A large number of new mammalian, insect and plant viruses were found, and Donaldson also discovered a new strain of coronavirus.

In 2013, Yang Fanli et al. applied a viral macrogenomics approach to study new viruses such as bat group 1 small bipartite RNA viruses and circoviruses collected in Jilin, Yunnan and Hunan.

Ebola virus was characterized by viral macrogenomics method in 2000

From this, it can be learned that emerging viruses in latency can be detected