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CORD-19:d0d330fbfb644da246909905d6537021f7393661 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-34 Sentence denotes viruses Bat Coronaviruses in China
T2 36-44 Sentence denotes Abstract
T3 45-294 Sentence denotes During the past two decades, three zoonotic coronaviruses have been identified as the cause of large-scale disease outbreaks-Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Swine Acute Diarrhea Syndrome (SADS).
T4 295-465 Sentence denotes SARS and MERS emerged in 2003 and 2012, respectively, and caused a worldwide pandemic that claimed thousands of human lives, while SADS struck the swine industry in 2017.
T5 466-634 Sentence denotes They have common characteristics, such as they are all highly pathogenic to humans or livestock, their agents originated from bats, and two of them originated in China.
T6 635-807 Sentence denotes Thus, it is highly likely that future SARS-or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China.
T7 808-993 Sentence denotes Therefore, the investigation of bat coronaviruses becomes an urgent issue for the detection of early warning signs, which in turn minimizes the impact of such future outbreaks in China.
T8 994-1256 Sentence denotes The purpose of the review is to summarize the current knowledge on viral diversity, reservoir hosts, and the geographical distributions of bat coronaviruses in China, and eventually we aim to predict virus hotspots and their cross-species transmission potential.
T9 1258-1530 Sentence denotes Fifteen years after the first highly pathogenic human coronavirus caused the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak, another severe acute diarrhea syndrome coronavirus (SADS-CoV) devastated livestock production by causing fatal diseases in pigs.
T10 1531-1616 Sentence denotes Both outbreaks began in China and were caused by coronaviruses of bat origin [1, 2] .
T11 1617-1744 Sentence denotes This increased the urgency to study bat coronaviruses in China to understand their potential of causing another virus outbreak.
T12 1745-1945 Sentence denotes In this review, we collected information from past epidemiology studies on bat coronaviruses in China, including the virus species identified, their host species, and their geographical distributions.
T13 1946-2051 Sentence denotes We also discuss the future prospects of bat coronaviruses cross-species transmission and spread in China.
T14 2052-2170 Sentence denotes Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae in the family Coronaviridae and the order Nidovirales.
T15 2171-2254 Sentence denotes CoVs have an enveloped, crown-like viral particle from which they were named after.
T16 2255-2390 Sentence denotes The CoV genome is a positive-sense, single-strand RNA (+ssRNA), 27-32 kb in size, which is the second largest of all RNA virus genomes.
T17 2391-2675 Sentence denotes Typically, two thirds of the genomic RNA encodes for two large overlapping polyproteins, ORF1a and ORF1b, that are processed into the viral Bat are the only mammals with the capability of powered flight, which enables them to have a longer range of migration compared to land mammals.
T18 2676-2812 Sentence denotes Bats are also the second largest order of mammals, accounting for about a fifth of all mammalian species, and are distributed worldwide.
T19 2813-3065 Sentence denotes Phylogenetic analysis classified bats into two large suborders-the Yinpterochiroptera, consisting of one Pteropodidae (megabat) and five Rhinolophoidea (microbat) families, and the Yangochiroptera comprising a total of thirteen microbat families [15] .
T20 3066-3265 Sentence denotes It is hypothesized that flight provided the selection pressure for coexistence with viruses, while the migratory ability of bats has particular relevance in the context of disease transmission [16] .
T21 3266-3361 Sentence denotes Indeed, bats were linked to a few highly pathogenic human diseases, supporting this hypothesis.
T22 3362-3648 Sentence denotes Some of these well characterized bat viruses, including bat lyssaviruses (Rabies virus), henipaviruses (Nipah virus and Hendra virus), CoVs (SARS-CoV, MERS-CoV, and SADS-CoV), and filoviruses (Marburg virus, Ebola virus, and Mengla virus), pose a great threat to human health [16, 17] .
T23 3649-3830 Sentence denotes A comprehensive analysis of mammalian host-virus relationships demonstrated that bats harbor a significantly higher proportion of zoonotic viruses than other mammalian orders [18] .
T24 3831-3898 Sentence denotes Viruses from most of the viral families can be found in bats [16] .
T25 3899-3971 Sentence denotes Bats are now recognized as important reservoir hosts of CoVs (Table 1) .
T26 3972-4149 Sentence denotes Although civet cats were initially identified as the animal origin of SARS-CoV, bats were soon found to be the most likely natural reservoir hosts of this virus [19] [20] [21] .
T27 4150-4333 Sentence denotes Long-term surveillance revealed an average 10% SARS-related CoV nucleotide positivity in bats, including some viruses that can use same human entry receptor ACE2 as SARS-CoV [7, 22] .
T28 4334-4489 Sentence denotes Similarly, bats have been proposed to harbor the progenitor viruses of MERS-CoV, although dromedary camels can transmit this virus to humans directly [9] .
T29 4490-4554 Sentence denotes The most recent SADS-CoV spillover was traced back to bats [2] .
T30 4555-4701 Sentence denotes In addition, bats also carry α-CoVs that are related to pathogenic human 229E-and NL63-CoVs, as well as pandemic swine coronavirus PEDV [23, 24] .
T31 4702-4838 Sentence denotes In summary, bats carry major α-(10 out of 17) and β-(7 out of 12) CoV species that may spillover to humans and cause disease (Table 1) .
T32 4839-4935 Sentence denotes Attributed to the wide distribution of bats, CoVs can be found worldwide, including China [25] .
T33 4936-5041 Sentence denotes Two bat CoVs caused outbreaks in China; it is thus urgent to study the reasons to avoid future outbreaks.
T34 5042-5129 Sentence denotes China is the third largest territory and is also the most populous nation in the world.
T35 5130-5359 Sentence denotes A vast homeland plus diverse climates bring about great biodiversity including that of bats and bat-borne viruses-most of the ICTV coronavirus species (22/38) were named by Chinese scientists studying local bats or other mammals.
T36 5360-5418 Sentence denotes The majority of the CoVs can be found in China (Table 1) .
T37 5419-5540 Sentence denotes Moreover, most of the bat hosts of these CoVs live near humans, potentially transmitting viruses to humans and livestock.
T38 5541-5670 Sentence denotes Chinese food culture maintains that live slaughtered animals are more nutritious, and this belief may enhance viral transmission.
T39 5671-5766 Sentence denotes It is generally believed that bat-borne CoVs will re-emerge to cause the next disease outbreak.
T40 5767-5809 Sentence denotes In this regard, China is a likely hotspot.
T41 5810-5908 Sentence denotes The challenge is to predict when and where, so that we can try our best to prevent such outbreaks.
T42 5910-6019 Sentence denotes In November 2012, the first case of SARS was recorded in Foshan city, Guangdong Province, China ( Figure 1 ).
T43 6020-6202 Sentence denotes In 2005, two independent Chinese groups reported the first bat SARS-related CoV (SARSr-CoV) that was closely related to human SARS-CoV, implying a bat origin of the latter [20, 21] .
T44 6203-6279 Sentence denotes Since then, more bat SARSr-CoV isolates were identified in China (Table 1) .
T45 6280-6461 Sentence denotes Genome identities of these bat SARSr-CoVs are as high as 92% to human SARS-CoV, but their major receptor binding spike proteins cannot use the human virus entry receptor ACE2 [67] .
T46 6462-6527 Sentence denotes Whether they are the progenitor viruses of SARS-CoV is debatable.
T47 6528-6666 Sentence denotes In 2013, the isolation of a bat SARSr-CoV that uses the ACE2 receptor provided the strongest evidence of the bat origin of SARS-CoV [22] .
T48 6667-6901 Sentence denotes Furthermore, the building blocks for SARS-CoV were identified from eleven different SARSr-CoV viral strains in a five-year surveillance program in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China [62] .
T49 6902-6970 Sentence denotes SARSr-CoVs found in China show great genomic diversity ( Figure 2 ).
T50 6971-7070 Sentence denotes Sequence identities of the conserved 440 bp RdRp region ranges from 80 to 100% with human SARS-CoV.
T51 7071-7312 Sentence denotes CoV diversity in bats is thought to be shaped by both species richness and geographical distribution, and CoVs exhibit clustering at the bat genera level, with these genus-specific clusters largely associated with distinct CoV species [25] .
T52 7313-7347 Sentence denotes Our analysis supports this theory.
T53 7348-7474 Sentence denotes SARSr-CoVs are present in different bat species but all belong to the family of Rhinolophidae and Hipposideridae ( Figure 1 ).
T54 7475-7662 Sentence denotes Chaerephon plicata bats were also reported as carriers in one study, but this cannot be conclusively supported without SARSr-CoVs found in China show great genomic diversity ( Figure 2 ).
T55 7663-7762 Sentence denotes Sequence identities of the conserved 440 bp RdRp region ranges from 80 to 100% with human SARS-CoV.
T56 7763-8004 Sentence denotes CoV diversity in bats is thought to be shaped by both species richness and geographical distribution, and CoVs exhibit clustering at the bat genera level, with these genus-specific clusters largely associated with distinct CoV species [25] .
T57 8005-8039 Sentence denotes Our analysis supports this theory.
T58 8040-8165 Sentence denotes SARSr-CoVs are present in different bat species but all belong to the family of Rhinolophidae and Hipposideridae (Figure 1 ).
T59 8166-8334 Sentence denotes Chaerephon plicata bats were also reported as carriers in one study, but this cannot be conclusively supported without molecular identification of the bat species [8] .
T60 8335-8673 Sentence denotes In China, horseshoe bat species (Rhinolophus spp.) are widely Viruses 2019, 11, 210 6 of 14 distributed, including R. sinicus, R. ferrumequinum, R. macrotis, R. pearsoni, and R. pusillus, and are also the most frequent SARSr-CoV carriers throughout the nation [7, 8, [20] [21] [22] 27, 40, 43, 45, 58, 59, [61] [62] [63] 68] ( Figure 1 ).
T61 8674-8752 Sentence denotes The most variable regions among bat SARSr-CoVs are the S and ORF8 genes [62] .
T62 8753-8878 Sentence denotes The S protein in certain strains is capable of using human ACE2 as a receptor and thus poses a direct threat to humans [69] .
T63 8879-9011 Sentence denotes Interestingly, all the SARSr-CoVs that are capable of using human ACE2 were found in R. sinicus in Yunnan Province [7, 22, 27, 62] .
T64 9012-9200 Sentence denotes Other SARSr-CoVs that cannot use human ACE2 were distributed in multiple provinces, from north Jilin, Shaanxi, Shanxi to south Hubei, Zhejiang, Yunnan, Guizhou, and Guangdong ( Figure 1 ).
T65 9201-9494 Sentence denotes Another protein, ORF8, was suggested to be important for interspecies transmission, as most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8 compared to civet SARSr-CoVs, which results in the formation of two separate open reading frames, ORF 8a and 8b [40] .
T66 9495-9694 Sentence denotes Only two R. ferrumequinum and one R. sinicus from Yunnan Province carried viruses that possess ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs [40, 62] .
T67 9695-9851 Sentence denotes It was strongly suggested that SARS-CoV most likely originated from Yunnan Rhinolophus bats via recombination events among existing SARSr-CoVs. (Figure 1 ).
T68 9852-9930 Sentence denotes The most variable regions among bat SARSr-CoVs are the S and ORF8 genes [62] .
T69 9931-10056 Sentence denotes The S protein in certain strains is capable of using human ACE2 as a receptor and thus poses a direct threat to humans [69] .
T70 10057-10189 Sentence denotes Interestingly, all the SARSr-CoVs that are capable of using human ACE2 were found in R. sinicus in Yunnan Province [7, 22, 27, 62] .
T71 10190-10378 Sentence denotes Other SARSr-CoVs that cannot use human ACE2 were distributed in multiple provinces, from north Jilin, Shaanxi, Shanxi to south Hubei, Zhejiang, Yunnan, Guizhou, and Guangdong ( Figure 1 ).
T72 10379-10671 Sentence denotes Another protein, ORF8, was suggested to be important for interspecies transmission, as most human SARS-CoV epidemic strains contain a signature 29nucleotide deletion in ORF8 compared to civet SARSr-CoVs, which results in the formation of two separate open reading frames, ORF 8a and 8b [40] .
T73 10672-10871 Sentence denotes Only two R. ferrumequinum and one R. sinicus from Yunnan Province carried viruses that possess ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs [40, 62] .
T74 10872-11015 Sentence denotes It was strongly suggested that SARS-CoV most likely originated from Yunnan Rhinolophus bats via recombination events among existing SARSr-CoVs.
T75 11016-11198 Sentence denotes These studies revealed that various SARSr-CoVs capable of using human ACE2 are still circulating among bats in China, highlighting the possibly of another SARS-like disease outbreak.
T76 11199-11259 Sentence denotes Certain areas in Yunnan Province are hotspots for spillover.
T77 11260-11431 Sentence denotes To support this hypothesis, we provide serological evidence of bat SARSr-CoV infection in humans in Yunnan Province where no prior exposure to SARS-CoV was recorded [70] .
T78 11432-11558 Sentence denotes The majority of the SARSr-CoVs appear not able to use ACE2, but their infectivity or pathogenesis to humans are still unknown.
T79 11559-11668 Sentence denotes Frequent interspecies recombination may result in another human infectious coronavirus from these SARSr-CoVs.
T80 11669-12059 Sentence denotes Furthermore, there are still unanswered questions about SARS, e.g., 'Why did the first SARS case occur in Guangdong Province, but all the human-ACE2-using SARSr-CoVs were found in Yunnan Province?' and 'Why does R. sinicus in certain areas carry human-ACE2-using SARSr-CoVs but no Notably, samples that were positive for BtMy-Sax11, BtNy-Sc13, and BtScCoV-512 were also identified in China.
T81 12060-12135 Sentence denotes These were not taken into account here as too few sequences were available.
T82 12136-12318 Sentence denotes These studies revealed that various SARSr-CoVs capable of using human ACE2 are still circulating among bats in China, highlighting the possibly of another SARS-like disease outbreak.
T83 12319-12379 Sentence denotes Certain areas in Yunnan Province are hotspots for spillover.
T84 12380-12551 Sentence denotes To support this hypothesis, we provide serological evidence of bat SARSr-CoV infection in humans in Yunnan Province where no prior exposure to SARS-CoV was recorded [70] .
T85 12552-12678 Sentence denotes The majority of the SARSr-CoVs appear not able to use ACE2, but their infectivity or pathogenesis to humans are still unknown.
T86 12679-12788 Sentence denotes Frequent interspecies recombination may result in another human infectious coronavirus from these SARSr-CoVs.
T87 12789-13199 Sentence denotes Furthermore, there are still unanswered questions about SARS, e.g., 'Why did the first SARS case occur in Guangdong Province, but all the human-ACE2-using SARSr-CoVs were found in Yunnan Province?' and 'Why does R. sinicus in certain areas carry human-ACE2-using SARSr-CoVs but no other Rhinolophus species carry the same viruses?' Above all, further extensive surveillance of SARSr-CoVs in China is warranted.
T88 13200-13299 Sentence denotes Different to bat SARSr-CoV, MERS-cluster CoVs were found in bats before the MERS disease outbreaks.
T89 13300-13418 Sentence denotes Two bat CoVs, Tylonycteris HKU4 and Pipistrellus HKU5 were first described as putative group 2c CoVs in 2006 in China.
T90 13419-13513 Sentence denotes They were associated with the HCoV-EMC (MERS-CoV) that started the 2012 pandemic [9, 38, 39] .
T91 13514-13718 Sentence denotes It is generally accepted that Middle East dromedary camels were the major animal source for the zoonotic transmission of human MERS, while bats harbor CoVs that shared common ancestry with MERS-CoV [71] .
T92 13719-13835 Sentence denotes Extensive global surveys revealed a wide distribution of largely diverged MERS-cluster CoVs (lineage 2c CoVs) [71] .
T93 13836-14047 Sentence denotes Two closely related Neoromicia zuluensis bat CoVs, NeoCoV and PREDICT/PDF-2180, were subsequently found, further supporting the idea that MERS-CoV was descended from an ancestral virus of African bats [72, 73] .
T94 14048-14159 Sentence denotes So far, three species of lineage 2c CoVs have been found in bats, according to the latest CoV taxonomy reports.
T95 14160-14347 Sentence denotes Based on phylogenetic trees constructed using RdRp, ORF1, S1, and N sequences, bat MERS-related CoVs (MERSr-CoVs) are the closest relatives of MERS-CoV, followed by HKU4-CoV and HKU5-CoV.
T96 14348-14442 Sentence denotes However, in the S1 region, MERS-CoV was much closer to HKU4-CoV than to MERSr-CoV or HKU5-CoV.
T97 14443-14679 Sentence denotes Likewise, pseudovirus assays showed that the MERSr-CoV (HKU25 and 422CoV) spike protein can use human DPP4 for entry into hDPP4-expressing cells, although with lower efficiency than that of MERS-CoV or HKU4-CoV spike proteins [49, 50] .
T98 14680-14749 Sentence denotes There is no evidence of HKU5-CoV using the human DPP4 receptor [74] .
T99 14750-14832 Sentence denotes All three types of bat MERS-cluster CoVs can be found in China (Figures 1 and 2) .
T100 14833-14897 Sentence denotes Their reservoir hosts all belong to the Vespertilionidae family.
T101 14898-15142 Sentence denotes MERSr-CoV can be found in multiple bat species, including Pipistrellus bats (P. abramus and P. pipistrellus), great evening bats (Ia io), particolored bats (Vespertilio superans), and Chinese pipistrelle bats (Hypsugo pulveratus) [49, 50, 52] .
T102 15143-15284 Sentence denotes Due to this wide host spectrum, MERSr-CoV also showed a large genetic diversity, ranging from 72 to 100% in the conserved 440 bp RdRp region.
T103 15285-15433 Sentence denotes In contrast, HKU4-CoVs were only carried by Tylonycteris bats (T. pachypus and T. robustula) and were relatively conserved [38, 39, 49] (Figure 2 ).
T104 15434-15564 Sentence denotes HKU5-CoVs were found in different Pipistrellus bats (P. abramus, P. pipistrellus, P. minus, and P. spp.) [8, 36, 38, 39, 49, 51] .
T105 15565-15616 Sentence denotes Like HKU4-CoVs, they are also relatively conserved.
T106 15617-15689 Sentence denotes The range of distribution varies, depending on MERS-cluster CoV species.
T107 15690-15815 Sentence denotes HKU5-CoVs should be the most widely distributed CoVs among the three as their hosts, Pipistrellus bats, live close to humans.
T108 15816-15972 Sentence denotes However, the reported CoV positive samples can only be found in Guangdong, Hong Kong, and Macau, possibly due to a lack of investigation in other provinces.
T109 15973-16109 Sentence denotes In contrast, MERSr-CoVs were reported in multiple bat species in Sichuan, Guangdong, and Hong Kong at a much lower level than HKU5-CoVs.
T110 16110-16325 Sentence denotes Similarly, Tylonycteris bats are a rare bat species that live in bamboo, which restricted the distribution of HKU4-CoVs to certain locations in Guangdong, Guangxi, Yunnan, Guizhou, Hong Kong, and Macau ( Figure 1 ).
T111 16326-16755 Sentence denotes To sum up, it appears that the risk of MERS-cluster CoV spillover to humans leading to an epidemic in China is low for the following reasons: (1) the geographical distribution of MERSr-CoVs and HKU4-CoVs that have the potential to infect humans (capable of using human entry receptors) is limited, and (2) HKU5-CoVs that widely exist in Chinese bats across the nation have not obtained the ability of using human entry receptors.
T112 16756-16909 Sentence denotes However, we should not underestimate the possibility of recombination among different bat CoVs that lead to the generation of potential pandemic viruses.
T113 16910-16964 Sentence denotes HKU2r-CoVs have only been reported in China and Kenya.
T114 16965-17165 Sentence denotes From studies in China, HKU2r-CoVs have been frequently found in Rhinolophus bats (R. affinis, R. sinicus, R. rex, and R. pusillus) in several provinces before the SADS outbreak [2, 7, 8, 38, 41, 44] .
T115 17166-17245 Sentence denotes So far, the virus has been reported in Hong Kong, Guangdong, Yunnan, and Tibet.
T116 17246-17352 Sentence denotes There are perhaps more to be discovered in other provinces considering the wide range of Rhinolophus bats.
T117 17353-17489 Sentence denotes Notably, these bat species, which constantly interact with both livestock and humans in China, also harbor SARSr-CoVs (see Section 3.1).
T118 17490-17572 Sentence denotes Likewise, HKU2r-CoVs showed a high genetic diversity with SARSr-CoVs ( Figure 2 ).
T119 17573-17688 Sentence denotes Due to these characteristics, HKU2r-CoVs were listed as viruses that were highly likely to cross species to humans.
T120 17689-17910 Sentence denotes The novel HKU2r-CoV, swine acute diarrhea syndrome coronavirus (SADS-CoV), was identified as the etiological agent responsible for a large-scale outbreak of fatal disease in pigs in China, Guangdong Province in 2017 [2] .
T121 17911-18077 Sentence denotes The entry receptor of SADS-CoV has not been identified, yet this virus showed a capacity for infecting a wide range of human, swine, and bat cells (unpublished data).
T122 18078-18241 Sentence denotes In China, the high density of pig farms and the wide distribution of host bat species promote the possibility of future HKU2r-CoV cross-species transmission [75] .
T123 18242-18328 Sentence denotes Thus, studies on bat HKU2r-CoVs spillover potential and their pathogenesis are urgent.
T124 18329-18462 Sentence denotes To predict the next CoV that will cause a virus outbreak in future, we list the general factors that may contribute to this outbreak.
T125 18463-18520 Sentence denotes Firstly, bats host a large number of highly diverse CoVs.
T126 18521-18649 Sentence denotes It is known that CoV genomes regularly undergo recombination during infection, and a rich gene pool can facilitate this process.
T127 18650-18720 Sentence denotes Secondly, bat species are widely distributed and live close to humans.
T128 18721-18775 Sentence denotes Thirdly, the viruses are pathogenic and transmissible.
T129 18776-18853 Sentence denotes In this context, SADS-CoV and SARS-CoV outbreaks in China are not unexpected.
T130 18854-18955 Sentence denotes By this model, there are other CoVs that have not yet caused virus outbreaks but should be monitored.
T131 18956-19135 Sentence denotes Within the family Vespertilionidae, the mouse-eared bats (Myotis) which favor roosting in abandoned human facilities are also a widespread genus of bats besides Pipistrellus bats.
T132 19136-19269 Sentence denotes They carry a large number and genetically diversified HKU6-CoVs that are closely related to Myotis ricketti α-CoV Sax-2011 [36, 38] .
T133 19270-19348 Sentence denotes Moreover, bent-winged bats (Miniopterus spp.) carry a large variety of α-CoVs.
T134 19349-19480 Sentence denotes One of the most frequently detected viruses is HKU8-CoV, which was first described circulating in M. pusillus in Hong Kong in 2005.
T135 19481-19697 Sentence denotes Later, it was also found in M. magnate, M. fuliginosus, and M. schreibersii in Hong Kong, Guangdong, Yunnan, Fujian, and Hubei provinces, showing a great genetic diversity [32] [33] [34] [35] 37, 41, 60] (Figure 1 ).
T136 19698-19862 Sentence denotes Besides HKU8-CoVs, bent-winged bats (Miniopterus spp.) also harbor a large amount of Miniopterus bat CoV 1 (BtMiCoV-1), which were called CoV1A or CoV1B previously.
T137 19863-20097 Sentence denotes This viral species was found almost as frequently as HKU8-CoV in multiple provinces in China in Miniopterus bats, although these viruses showed a relatively small sequence variation between each other [32] [33] [34] [35] 37, 41, 60] .
T138 20098-20303 Sentence denotes Genetic analysis indicates that BtMiCoV-1, HKU8-CoV, and HKU7-CoV (previous name) are different but closely related CoVs circulating in bent-winged bats and may have descended from a common ancestor [34] .
T139 20304-20394 Sentence denotes Additionally, Rousettus leschenaultii bats in the family of Pteropodidae harbor HKU9-CoVs.
T140 20395-20552 Sentence denotes As a fruit bat, Rousettus leschenaultii has a wider flying range than most of the insectivorous bats in China, thus it may carry viruses over long distances.
T141 20553-20687 Sentence denotes A comparison of the reported HKU9-CoV sequences showed a high genetic diversity within this viral species [55] [56] [57] ( Figure 2) .
T142 20688-20739 Sentence denotes The last CoV that should be mentioned is HKU10-CoV.
T143 20740-20912 Sentence denotes HKU10-CoVs can be found in bats from different genera (Rousettus leschenaultii and Hipposideros pomona), suggesting interspecies transmission between bats [7, 26, 27, 39] .
T144 20913-20990 Sentence denotes A genetic difference can also be observed for this virus species (Figure 2 ).
T145 20991-21100 Sentence denotes Above all, these viruses fit well in our SADS prediction model and should be monitored in our future studies.
T146 21101-21194 Sentence denotes In 2016, a novel β-CoV, Ro-BatCoVGCCDC1, was identified from the Rousettus leschenaultii bat.
T147 21195-21355 Sentence denotes However, we confirmed the host was a closely related Eonycteris spelaea bat upon species identification and then renamed the virus as BtEoCoV-GCCDC1 (Table 1 ).
T148 21356-21487 Sentence denotes The uniqueness of this virus is that it contains a gene that most likely originated from the p10 gene of a bat orthoreovirus [53] .
T149 21488-21587 Sentence denotes A two-year follow-up study also illustrated that BtEoCoV-GCCDC1 persistently circulates among bats.
T150 21588-21679 Sentence denotes Different to the genetically diverged HKU9-CoV, this virus is highly conserved (Figure 2 ).
T151 21680-21757 Sentence denotes BtEoCoV-GCCDC1 has only been found in south Yunnan Province so far [54, 55] .
T152 21758-21831 Sentence denotes In addition, there are other bat CoVs that have been identified in China:
T153 21832-22129 Sentence denotes Rhinolophus ferrumequinum α-CoV HuB-2013 [8] , Myotis ricketti α-CoV Sax-2011 [8, 37] , Nyctalus velutinus α-CoV SC-2013 [8] , Scotophilus bat CoV 512 [37] , Hipposideros bat β-CoV Zhejiang2013, and a Murina leucogaster bat CoV, which has been described as the evolutionary ancestor of PEDV [37] .
T154 22130-22302 Sentence denotes Notably, there are still many unclassified bat CoVs circulating in China, particularly in the northern part of the nation where bat viruses were rarely studied (Figure 1 ).
T155 22303-22442 Sentence denotes According to the criteria defined by the ICTV, the CoV family will most likely expand following further investigation of bat CoVs in China.
T156 22443-22537 Sentence denotes The coexistence of more than two viruses in the same bat is quite common for some bat species.
T157 22538-22641 Sentence denotes The coexistence of Miniopterus bat CoV 1 and HKU8-CoV in one bat has been frequently reported [7, 34] .
T158 22642-22788 Sentence denotes Another example is the coexistence between Rhinolophus HKU2-CoVs (SADS-CoV) and SARSr-CoVs that caused the virus outbreaks, respectively [2, 45] .
T159 22789-22887 Sentence denotes Real-time monitoring this bat genus is necessary for the prevention of future SARS-like outbreaks.
T160 22888-22999 Sentence denotes Moreover, two or more distinct genotypes of HKU9-CoVs were reported to coexist in a single Rousettus bat [56] .
T161 23000-23195 Sentence denotes The coexistence of HKU9-CoVs and a new identified bat filovirus (Mengla virus) that is phylogenetically related to the Ebola and Marburg viruses was also identified from Rousettus bats [17, 55] .
T162 23196-23355 Sentence denotes Given that a bat orthoreovirus p10 gene was incorporated in the BtEoCoV-GCCDC1 genome, recombination between the bat filovirus and HKU9-CoV cannot be excluded.
T163 23356-23544 Sentence denotes Other pairs were also recorded-HKU8-CoV with unclassified α-CoV [7] , HKU2-CoV with unclassified α-CoV [7] , HKU10-CoV with unclassified β-CoV [7] , and HKU6-CoV with bat adenovirus [36] .
T164 23545-23690 Sentence denotes Two bat origin CoVs caused large-scale epidemics in China over fourteen years, highlighting the risk of a future bat CoV outbreak in this nation.
T165 23691-23978 Sentence denotes In this review, we have summarized the current findings related to bat CoV epidemiology in China, aiming to explore the associations between CoV species, bat species, and geographical locations, and eventually we aim to predict the cross-species transmission potential of these bat CoVs.
T166 23979-24053 Sentence denotes Admittedly, the analysis may be affected by inaccurate or incomplete data.
T167 24054-24188 Sentence denotes For example, not all research groups performed bat species identification or used Global Positioning System (GPS) during bat sampling.
T168 24189-24250 Sentence denotes Bats in the north or west provinces were not surveyed either.
T169 24251-24335 Sentence denotes Nonetheless, we believe this analysis is a good starting point for further research.
T170 24336-25000 Sentence denotes Moreover, there are other outstanding questions that should be addressed in future studies: (1) given that most of the ICTV classified CoV species are from bats, why there are so many genetically divergent CoVs in bats, (2) the pathogenesis of most bat CoVs in humans remains unknown as the viruses have never been isolated or rescued-apart from the viruses identified during the outbreaks, many viruses pose a threat to human health, (3) although SARS-CoV and SADS-CoV were known to be transmitted from bats to human or swine, their exact transmission routes are unknown, and (4) why bats can maintain CoVs long-term without showing clinical symptoms of diseases.
T171 25001-25047 Sentence denotes A unique bat immunity model has been proposed.
T172 25048-25277 Sentence denotes The authors have shown that constitutively expressed bat interferon α may protect bats from infection [76] , while some particularly dampened immune pathways may allow bats to have a higher tolerance against viral diseases [77] .
T173 25278-25448 Sentence denotes While we start to unveil the mystery of unique bat immunity, there is still long way to go before we can fully understand the relationship between bats and coronaviruses.
T174 25449-25507 Sentence denotes Author Contributions: P.Z. and Z.-L.S. designed the study.
T175 25508-25540 Sentence denotes Y.F. and K.Z. analyzed the data.
T176 25541-25579 Sentence denotes P.Z. and Y.F. prepared the manuscript.