Preplanned Studies: A Landscape Analysis on Virus: based on NCBI Database

According to ‎the International Committee on Taxonomy of Viruses Master Species List 2020, more than 9,000 virus species have been identified on earth (1), of which the World Health Organization (WHO) announced that more than 200 species were known as zoonotic viruses (2). Previous studies have also shown that zoonoses (hantavirus, Ebola virus, highly pathogenic avian influenza, West Nile virus, Rift Valley fever virus, norovirus, severe acute respiratory syndrome coronavirus 1, Marburg virus, influenza A virus) infected more than 2.5 billion people every year, among which 2.7 million died (3). Zoonotic viruses have aroused broad concerns in recent years so that people have been encouraged to avoid eating wild animals, and a series of animal protection laws and regulations were enacted, such as the Convention on International Trade in Endangered Species of Wild Fauna and Flora (4). Researchers from different fields and countries have tried to collaborate to explore virus associations between animals and humans worldwide (5). However, many studies only focused on investigating a specific virus when it received enough attention as in a localized or global epidemic, such as Ebola virus, H1N1, Zika virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (6). Even so, it’s difficult for people to know exactly when, where and how the virus jumped from animal or environment to humans because it is impossible to design an observational study on the whole landscape around a virus. To understand the overall evolution law of viruses, this study aimed to find the spatial and temporal distribution of viruses and related hosts through the public database.

The National Center for Biotechnology Information (NCBI) virus database is a database of gene sequences maintained by the National Institutes of Health that aggregates and annotates all publicly available nucleotide and protein sequences, and it has been used for studies exploring quantitative snapshots of viral genomic trends and overviewing virus real-time quantitative polymerase chain reaction (RT-qPCR) method performance (7-8). In this study, we performed a spatiotemporal analysis on the viruses in the NCBI database and tried to disclose the potential time, place, and hosts that the virus appeared or stayed in their long evolutionary history. Our study indicated the top five widely distributed viruses and found that no virus had been reported in all countries/regions. In addition, the reported areas of viruses did not completely overlap with areas where their suspected hosts live. We also found that the 249 viruses isolated from humans were also isolated from 705 other mammals and 938 non-mammals. We attempted to map the distribution and evolution of viruses and identify suspected hosts globally based on the NCBI database, which was helpful for understanding the risk of virus infection in humans and was also a cost-effective method for monitoring and predicting public health and safety events globally.

The data were downloaded from the NCBI Virus database and covered available data up to September 2021 (www.ncbi.nlm.nih.gov/labs/virus). The data included virus genomic sequence submission information (accession number, submitter, and release date), virus types (species, genus, and family), and biological sample description (location, organisms of sample, isolation, and collection date). Data that were duplicated, missing, or had unidentified collected dates, locations, or organisms of the biological samples were excluded. Because the NCBI only reported that the virus was isolated from an organism, not whether the organism was the host of the virus, we referred to the organisms as suspected hosts. Based on the standard of NCBI taxonomy, suspected hosts were classified into animals, plants, and microbes.

The numbers were calculated by virus species, suspected hosts, suspected host locations, and collection time. The spatiotemporal distribution was mapped in country/region units and the path was analyzed by linking the reported location of the viruses or suspected hosts. Potential zoonotic diseases were explored by observing the suspected hosts from which the viruses were isolated.

All statistical analyses were performed in R statistical software (version 4.1.0, The R Foundation for Statistical Computing, Vienna, Austria). Animal silhouettes representing hosts were downloaded from PhyloPic (http://www.phylopic.org). All maps were made by using ArcGIS (version 10.7, Esri Inc, Redlands, CA, USA).

A total of 605,504 records covering 24,234 viruses from 240 countries/regions with sample collection date from 1865 to September 22, 2021 were involved in the final analysis. We observed that 12,243 viruses were isolated from 4,187 animals, 2,856 from 2,074 plants, and 9,176 from 965 microbes (Figure 1). However, more than 90% viruses (21,845 of 24,234) were reported in a single country/region, and the remaining 10% (2,389 of 24,234) of viruses were from 236 countries/regions and were isolated from 4,742 suspected hosts in 238 countries/regions.

Figure 1. 

Flow diagram depicting the process of identification and inclusion of selected records.

Abbreviation: NCBI=National Center for Biotechnology Information.

The top five widely distributed viruses were influenza A virus, human immunodeficiency virus 1, hepatitis B virus, rabies lyssavirus, dengue virus, and measles morbillivirus (dengue virus and measles morbillivirus tied for fifth place), which were reported in 155, 151, 145, 128, 122, and 122 countries/regions, respectively (Supplementary Table S1). Influenza A virus was reported over approximately 118 years, ranging from the first report in Italy in 1902 to the last report in Tanzania in 2020, and was reported in 155 countries/regions from 422 suspected hosts living in 231 countries/regions. Human immunodeficiency virus 1 was reported over approximately 120 years, ranging from Russia in 1899 to Iraq in 2019, and was reported in 151 countries/regions from 1 suspected host (Homo sapiens) in 225 countries/regions; Hepatitis B virus was reported over approximately 120 years, ranging from Indonesia in 1900 to Ireland in 2020, and was reported in 145 countries/regions from 35 suspected hosts in 229 countries/regions; Rabies lyssavirus was reported over approximately 138 years, ranging from France in 1882 to Equatorial Guinea in 2020, and was reported in 128 countries/regions from 192 suspected hosts in 233 countries/regions; Dengue virus was reported over approximately 75 years, ranging from Colombia in 1944 to Sudan in 2019, and was reported in 122 countries/regions from 25 suspected hosts in 227 countries/regions; Measles morbillivirus was reported over approximately 101 years, ranging from New Zealand in 1919 to United Arab Emirates 2020, and was reported in 122 countries/regions from 3 suspected hosts (Chlorocebus aethiops, Homo sapiens, and Macaca fascicularis) in 225 countries/regions (Figure 2, Supplementary Figure S1A).

Figure 2. 

Coexisting virus species among animals, plants, and microbes. (A1) The number and intersection of virus species reported from NCBI Virus Database between 1865 and 2021/9. (A2) First reported host family sorted by first report time among coexisting virus species; (B) Coexisting virus species between Homo sapiens and animals, plants, or microbes.

Notes: The host families represented by the tags were shown in Supplementary Table S4, available in http://weekly.chinacdc.cn/.

The top five widely distributed suspected hosts were Homo sapiens, Bos taurus, Canis lupus familiaris, Gallus gallus, and Sus scrofa, which were reported in 225, 143, 123, 122 and 110 countries/regions, respectively (Supplementary Table S1). Homo sapiens were reported in 225 countries/regions in the past 154 years (from the United States in 1866 to the Faroe Islands in 2020), and approximately 1,075 viruses were isolated from this host. Bos taurus were reported in 143 countries/regions during the past 138 years (from France in 1882 to Luxembourg in 2020) and from which 273 viruses were isolated; Canis lupus familiaris were reported in 123 countries/regions during the past 89 years (from China in 1931 to Ghana in 2020) and from which 106 viruses were isolated; Gallus gallus were reported in 122 countries/regions during the past 118 years (from Italy in 1902 to Timor-Leste in 2020) and from which 287 viruses were isolated; Sus scrofa were reported in 110 countries/regions during the past 99 years (from China in 1921 to Paraguay in 2020) and from which 276 viruses were isolated (Supplementary Figure S1B).

There were 27 viruses in the database reported to be isolated from animals as well as plants (animals-plants). Similarly, 9 and 5 viruses were isolated from animals-microbes and plants-microbes, respectively (Figure 3A). Specifically, 249 viruses from humans were also isolated from the other 1,643 animals, among which 705 were mammals. Most of the 249 multi-suspected host viruses were reported in the United States (125 of 249), China (141 of 249), and Brazil (107 of 249), with 402, 344, and 187 suspected hosts, respectively (Figure 3B). The first reported human-animal multi-suspected host virus was the Vaccinia virus, isolated from Homo sapiens in the United States in 1866 (Supplementary Table S2).

In the study period, 181 countries/regions reported at least 1 new virus. The top 5 countries reporting the highest number of new virus species were the United States, China, Brazil, Australia, and Italy, with 6,628, 4,518, 1,032, 994, and 730 new virus species, respectively. Newly reported viruses showed a rapid increase since 2003, peaking in 2013, and then showed a jump decline until the bottom of 2019 (Supplementary Figure S2). In 2021, 14 new viruses were reported, of which Belarus, Canada, South Africa, the Republic of Korea, Spain, and Switzerland reported 1 new virus, Vietnam reported 2 new viruses, and the United States and China both reported 3 new virus species (Supplementary Table S3).