Bat coronavirus RaTG13 is a SARS-like

betacoronavirus ''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera (''Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part). ...

that infects the horseshoe bat '' Rhinolophus affinis''. It was discovered in 2013 in bat droppings from a mining cave near the town of Tongguan in Mojiang county in

Yunnan Yunnan , () is a landlocked Provinces of China, province in Southwest China, the southwest of the People's Republic of China. The province spans approximately and has a population of 48.3 million (as of 2018). The capital of the province is ...

China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...

. In February 2020, it was identified as the closest known (at the time) relative of

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

, the virus that causes

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

, sharing 96.1% nucleotide similarity. However, in 2022, scientists found three closer matches in bats found 530 km south, in Feuang, Laos, designated as BANAL-52 (96.8% similarity), BANAL-103 and BANAL-236.

History

In spring 2012, three miners cleaning bat feces in an abandoned copper mine near the town of Tongguan in

Mojiang Hani Autonomous County Mojiang Hani Autonomous County (; Hani: ) is an autonomous county under the jurisdiction of Pu'er City, in the south of Yunnan Province, China. Administrative divisions In the present, Mojiang Hani Autonomous County has 12 towns, 2 townships and ...

developed fatal

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...

. Out of concerns that the miner's cases could represent a novel disease, serum samples collected from the miners were sent to the

Wuhan Institute of Virology The Wuhan Institute of Virology, Chinese Academy of Sciences (WIV; ) is a research institute on virology administered by the Chinese Academy of Sciences (CAS), which reports to the State Council of the People's Republic of China. The institute ...

and tested by

Shi Zhengli Shi Zhengli (; born 26 May 1964) is a Chinese virologist who researches SARS-like coronaviruses of bat origin. Shi directs the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology (WIV). In 2017, Shi and her colleague Cui ...

and her group for

Ebola virus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and ot ...

Nipah virus Nipah virus, scientific name ''Nipah henipavirus'', is a bat-borne virus that causes Nipah virus infection in humans and other animals, a disease with a high mortality rate. Numerous disease outbreaks caused by Nipah virus have occurred in Sout ...

, and bat SARSr-CoV Rp3. The samples tested negative. In order to discover the possible cause of the infection, different animals (including bats, rats, and musk shrews) were sampled in and around the mining cave. Between 2012 and 2015, Shi Zhengli and her group isolated 293 diverse

coronaviruses Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the com ...

(284 alphacoronaviruses and 9

betacoronaviruses ''Betacoronavirus'' (β-CoVs or Beta-CoVs) is one of four genera ('' Alpha''-, ''Beta-'', '' Gamma-'', and '' Delta-'') of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals (of which humans are part ...

) from bat feces samples in the cave. One of the samples collected in 2013 from ''Rhinolophus affinis'' bat feces was the bat coronavirus RaTG13. The strain name was derived from the originating bat species, geographic location, and year collected. In 2020, Shi and her group retested the serum samples from the miners for SARS-CoV-2. The samples tested negative. In 2020, the virus was renamed from the original Ra4991 to RatG13, to reflect the species of bat from which the virus was collected (''Rhinolophus affinis''), the location where it was collected (Tongguan) and the year of the sample’s collection (2013). The change of name of the virus has been considered as innuendo by lab leak advocates.

Virology

RaTG13 is a

positive-strand RNA virus Positive-strand RNA viruses (+ssRNA viruses) are a group of related viruses that have positive-sense, single-stranded genomes made of ribonucleic acid. The positive-sense genome can act as messenger RNA (mRNA) and can be directly translated int ...

with an outer membrane. Its genome is approximately 29,800 nucleotides. The genome encodes a replicase (ORF1a/1b) and four structural proteins; including a

spike protein In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an enveloped virus. as cited in The proteins are usually glycoproteins that form dimers or ...

(S),

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

(M),

envelope protein A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...

(E) and nucleocapsid protein (N); and five

viral accessory protein A viral regulatory and accessory protein is a type of viral protein A viral protein is both a component and a product of a virus. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, n ...

s, including

ORF3a ORF3a (previously known as X1 or U274) is a gene found in coronaviruses of the subgenus ''Sarbecovirus'', including SARS-CoV and SARS-CoV-2. It encodes an accessory protein about 275 amino acid residues long, which is thought to function as a v ...

(NS3),

ORF6 ORF6 is a gene that encodes a viral accessory protein in coronaviruses of the subgenus '' Sarbecovirus'', including SARS-CoV and SARS-CoV-2. It is not present in MERS-CoV. It is thought to reduce the immune system response to viral infection t ...

(NS6),

ORF7a ORF7a (also known by several other names, including SARS coronavirus X4, SARS-X4, ORF7a, or U122) is a gene found in coronaviruses of the ''Betacoronavirus'' genus. It gene expression, expresses the Betacoronavirus NS7A protein, a type I transmem ...

(NS7a),

ORF7b ORF7b is a gene found in coronaviruses of the genus '' Betacoronavirus'', which expresses the accessory protein Betacoronavirus NS7b protein. It is a short, highly hydrophobic transmembrane protein of unknown function. Structure ORF7b protein ...

(NS7b) and

ORF8 ORF8 is a gene that encodes a viral accessory protein, Betacoronavirus NS8 protein, in coronaviruses of the subgenus ''Sarbecovirus''. It is one of the least well conserved and most variable parts of the genome. In some viruses, a deletion sp ...

(NS8). RaTG13 bears strong resemblance to the

virus (it shares 96.1% nucleotide similarity), and its existence is a supporting piece of evidence for SARS-CoV-2's natural origin. The difference between RaTG13 and SARS-CoV-2 is in the receptor-binding domain (RBD) of the spike protein (S), which is the portion that binds to the receptor protein on the surface of the

host cell In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' (symbiont). The guest is typically provided with nourishment and shelter. Examples include a ...

and causes infection, indicating that the RaTG13 virus might not use

angiotensin-converting enzyme 2 Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 a ...

(ACE2) as its entry site into the cell as does SARS-CoV-2. Further, the S protein of RaTG13 virus lacks the

furin Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these s ...

cleavage motif RRAR↓S. The binding affinity between RATG13 and hACE2 is lower than that between SARS-CoV-2 RBD and hACE2.

Phylogenetics

Phylogenetic tree

References

{{Coronaviridae SARS-CoV-2 Bat virome Coronaviridae Animal virology Sarbecovirus Zoonoses

History

Virology

Phylogenetics

Phylogenetic tree

See also

References