/random/ - random

Funding Agency

Agency

National Institute of Health (NIH)

Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Type

Research Project (R01)

Project #

5R01AI110964-03

Application #

9086286

Study Section

Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)

Program Officer

Stemmy, Erik J

Project Start

2014-06-01

Project End

2019-05-31

Budget Start

2016-06-01

Budget End

2017-05-31

Support Year

3

Fiscal Year

2016

Total Cost

Indirect Cost

Institution

Name

Ecohealth Alliance, Inc.

Department

Type

DUNS #

077090066

City

New York

State

NY

Country

United States

Zip Code

10001

Related projects

NIH 2019

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc.

NIH 2018

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc.

NIH 2017

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc. $597,112

NIH 2016

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc.

NIH 2015

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc. $630,445

NIH 2014

R01 AI Understanding the Risk of Bat Coronavirus Emergence

Daszak, Peter / Ecohealth Alliance, Inc. $666,442

Luo, Yun; Li, Bei; Jiang, Ren-Di et al. (2018) Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016. Virol Sin 33:87-95

Zhou, Peng; Fan, Hang; Lan, Tian et al. (2018) Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556:255-258

Wu, Zhiqiang; Lu, Liang; Du, Jiang et al. (2018) Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases. Microbiome 6:178

Wang, Ning; Li, Shi-Yue; Yang, Xing-Lou et al. (2018) Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virol Sin 33:104-107

Eskew, Evan A; Olival, Kevin J (2018) De-urbanization and Zoonotic Disease Risk. Ecohealth 15:707-712

Field, Hume Ernest (2018) Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa. Zoonoses Public Health :

Luo, Chu-Ming; Wang, Ning; Yang, Xing-Lou et al. (2018) Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus. J Virol 92:

Hu, Ben; Zeng, Lei-Ping; Yang, Xing-Lou et al. (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13:e1006698

Olival, Kevin J; Hosseini, Parviez R; Zambrana-Torrelio, Carlos et al. (2017) Host and viral traits predict zoonotic spillover from mammals. Nature 546:646-650

Olival, Kevin J; Willoughby, Anna R (2017) Prioritizing the 'Dormant' Flaviviruses. Ecohealth 14:1-2

Luo, Yun; Li, Bei; Jiang, Ren-Di et al. (2018) Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province, China During 2009-2016. Virol Sin 33:87-95

Zhou, Peng; Fan, Hang; Lan, Tian et al. (2018) Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 556:255-258

Wu, Zhiqiang; Lu, Liang; Du, Jiang et al. (2018) Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases. Microbiome 6:178

Wang, Ning; Li, Shi-Yue; Yang, Xing-Lou et al. (2018) Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virol Sin 33:104-107

Eskew, Evan A; Olival, Kevin J (2018) De-urbanization and Zoonotic Disease Risk. Ecohealth 15:707-712

Field, Hume Ernest (2018) Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa. Zoonoses Public Health :

Luo, Chu-Ming; Wang, Ning; Yang, Xing-Lou et al. (2018) Discovery of Novel Bat Coronaviruses in South China That Use the Same Receptor as Middle East Respiratory Syndrome Coronavirus. J Virol 92:

Hu, Ben; Zeng, Lei-Ping; Yang, Xing-Lou et al. (2017) Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 13:e1006698

Olival, Kevin J; Hosseini, Parviez R; Zambrana-Torrelio, Carlos et al. (2017) Host and viral traits predict zoonotic spillover from mammals. Nature 546:646-650

Olival, Kevin J; Willoughby, Anna R (2017) Prioritizing the 'Dormant' Flaviviruses. Ecohealth 14:1-2

>>62752

>>62753

>>62756

>>62754

> A combined modeling approach will include phylogenetic analyses of host receptors and novel CoV genes (including functional receptor binding domains)

>>62752

>>62753

>>62756

>>62754

> A combined modeling approach will include phylogenetic analyses of host receptors and novel CoV genes (including functional receptor binding domains)

>>62752

>>62753

>>62756

>>62754

> A combined modeling approach will include phylogenetic analyses of host receptors and novel CoV genes (including functional receptor binding domains)

>>62759

>>62757

>>62758

>>62759

>>62757

>>62758

>>62759

>>62757

>>62758

:(

Prioritizing the 'Dormant' Flaviviruses.

>Our global approach to emerging infectious disease research has been reactive for too long, with an increase in scientific investigations and funding (e.g., for surveillance, experimental studies, or countermeasures) only coming after international spread. González-Salazar et al.’s manuscript in this issue (2017) uses an ecological niche modeling approach to identify potential, currently unrecognized, vertebrate hosts for Zika virus in Mexico. This is an interesting approach to help target zoonotic disease surveillance in the animals that may serve as most likely natural reservoirs, and a good start. We need more analytical tools like this. We know virtually nothing about the sylvatic cycle, the vectors, the non-human reservoirs, or the general ecology of Zika. International efforts to map the potential distribution of Zika are focused on Aedes aegypti and A. albopictus, but we lack knowledge on the 17 other mosquito species that have been tested positive over the years, nor what other viruses these vectors may carry.

We need more predictive tools to forecast the risk that viruses pose before they become epidemics or pandemics. We need creative approaches, and multi-disciplinary collaborations to develop these sets of tools. Mathematical modelers need to work with field scientists, clinicians, bioinformaticians, virologists, and veterinarians, and we all need to collaborate more with laboratory scientists who can design experiments to validate our models. If phylogenetic and structural models predict an increase in host range for a virus, how can we design in vitro or in vivo experiments to test this? How can we make the most of the scattered information available on host range, vector range, and viral biology from the last 70+ years of disjunct studies to better prioritize the 53 known flaviviruses for future research? Yaounde virus, Kedougou virus, and Sepik virus are hardly household names, but they are the closest known relatives to viruses we know well—West Nile, Zika, Yellow Fever. How many more flaviviruses will we discover in ecosystems around the world if we make a concerted effort to find them? How can we then include these novel viruses into our prioritization schemes?

>Just as weather forecasting seemed like an impossibility before the advent of satellites, computer algorithms, and telecommunication equipment, to some naysayers the era of pandemic forecasting may seem impossible, or a very a long way off. It is not. We are in this era now, but these are still early days. A growing and diverse community of scientists are working hard each day to build and experiment with tools to forecast and prevent emerging viruses. Many of these analytics can be applied directly, right now, to improve public health. For example, they can identify geographic regions, host species, host traits, vectors, and viral traits that rank their likelihood of disease emergence. This allows agencies to target how they prioritize field surveillance or prioritize which viruses we should research more before they infect humans on a wide scale. They can also start to estimate how many other unique flaviviruses are out there on the planet so that we can begin to catalog and characterize them all. These messages should not be lost in our rush to focus on the current public health emergency. Part of our public health response should be to set research priorities for those quiescent viruses we already know about before they become the next Zika.

>An international journal at the interface of ecology, health sciences and sustainability

Addresses health and sustainability challenges within diverse settings, ranging from public health practice and human and veterinary medicine, to conservation and ecosystem management, to rural and urban development and planning

Editor-In-Chief: Peter Daszak, EcoHealth Alliance, New York, USA

>Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrelluscoronavirus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV.IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.

https://pubmed.ncbi.nlm.nih.gov/29669833/

FIG 5 BtCoV/Ii/GD/2014-422 spike-mediated pseudovirus entry and inhibition assay. Anti-hDPP4 antibodies competitively block interactions between BtCoV/Ii/GD/2014-422 spike and hDPP4 but not bat DPP4. Error bars indicate SEM (*, P < 0.05 by two-tailed t test; n = 4). (A) Anti-hDPP4 antibodies did not neutralize BtCoV/Ii/GD/2014-422 spike-mediated and MERS-CoV spike-mediated pseudovirus entry into bDPP4-expressing cells. (B) Anti-hDPP4 antibodies strongly neutralized BtCoV/Ii/GD/2014-422 spike-mediated and MERS-CoV spike-mediated pseudovirus entry into hDPP4-expressing Tb1-Lu cells.

FIG 5 BtCoV/Ii/GD/2014-422 spike-mediated pseudovirus entry and inhibition assay. Anti-hDPP4 antibodies competitively block interactions between BtCoV/Ii/GD/2014-422 spike and hDPP4 but not bat DPP4. Error bars indicate SEM (*, P < 0.05 by two-tailed t test; n = 4). (A) Anti-hDPP4 antibodies did not neutralize BtCoV/Ii/GD/2014-422 spike-mediated and MERS-CoV spike-mediated pseudovirus entry into bDPP4-expressing cells. (B) Anti-hDPP4 antibodies strongly neutralized BtCoV/Ii/GD/2014-422 spike-mediated and MERS-CoV spike-mediated pseudovirus entry into hDPP4-expressing Tb1-Lu cells.

>>62767

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH

>How many more flaviviruses will we discover in ecosystems around the world if we make a concerted effort to find them?

>>62764

>How many more flaviviruses will we discover in ecosystems around the world if we make a concerted effort to find them?

>>62764

>Project Summary: Understanding the Risk of Bat Coronavirus Emergence Novel zoonotic, bat-origin CoVs are a significant threat to global health and food security, as the cause of SARS in China in 2002, the ongoing outbreak of MERS, and of a newly emerged Swine Acute Diarrhea Syndrome in China. In a previous R01 we found that bats in southern China harbor an extraordinary diversity of SARSr-CoVs, some of which can use human ACE2 to enter cells, infect humanized mouse models causing SARS-like illness, and evade available therapies or vaccines. We found that people living close to bat habitats are the primary risk groups for spillover, that at one site diverse SARSr-CoVs exist that contain every genetic element of the SARS-CoV genome, and identified serological evidence of human exposure among people living nearby. These findings have led to 18 published peer-reviewed papers, including two papers in Nature, and a review in Cell. Yet salient questions remain on the origin, diversity, capacity to cause illness, and risk of spillover of these viruses. In this R01 renewal we will address these issues through 3 specific aims: Aim 1. Characterize the diversity and distribution of high spillover-risk SARSr-CoVs in bats in southern China. We will use phylogeographic and viral discovery curve analyses to target additional bat sample collection and molecular CoV screening to fill in gaps in our previous sampling and fully characterize natural SARSr-CoV diversity in southern China. We will sequence receptor binding domains (spike proteins) to identify viruses with the highest potential for spillover which we will include in our experimental investigations (Aim 3). Aim 2. Community, and clinic-based syndromic, surveillance to capture SARSr-CoV spillover, routes of exposure and potential public health consequences. We will conduct biological-behavioral surveillance in high-risk populations, with known bat contact, in community and clinical settings to 1) identify risk factors for serological and PCR evidence of bat SARSr-CoVs; & 2) assess possible health effects of SARSr-CoVs infection in people. We will analyze bat-CoV serology against human-wildlife contact and exposure data to quantify risk factors and health impacts of SARSr-CoV spillover. Aim 3. In vitro and in vivo characterization of SARSr-CoV spillover risk, coupled with spatial and phylogenetic analyses to identify the regions and viruses of public health concern. We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential. We will combine these data with bat host distribution, viral diversity and phylogeny, human survey of risk behaviors and illness, and serology to identify SARSr-CoV spillover risk hotspots across southern China. Together these data and analyses will be critical for the future development of public health interventions and enhanced surveillance to prevent the re-emergence of SARS or the emergence of a novel SARSr-CoV.

https://taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01AI110964&arg_ProgOfficeCode=104

>Project Summary: Understanding the Risk of Bat Coronavirus Emergence Novel zoonotic, bat-origin CoVs are a significant threat to global health and food security, as the cause of SARS in China in 2002, the ongoing outbreak of MERS, and of a newly emerged Swine Acute Diarrhea Syndrome in China. In a previous R01 we found that bats in southern China harbor an extraordinary diversity of SARSr-CoVs, some of which can use human ACE2 to enter cells, infect humanized mouse models causing SARS-like illness, and evade available therapies or vaccines. We found that people living close to bat habitats are the primary risk groups for spillover, that at one site diverse SARSr-CoVs exist that contain every genetic element of the SARS-CoV genome, and identified serological evidence of human exposure among people living nearby. These findings have led to 18 published peer-reviewed papers, including two papers in Nature, and a review in Cell. Yet salient questions remain on the origin, diversity, capacity to cause illness, and risk of spillover of these viruses. In this R01 renewal we will address these issues through 3 specific aims: Aim 1. Characterize the diversity and distribution of high spillover-risk SARSr-CoVs in bats in southern China. We will use phylogeographic and viral discovery curve analyses to target additional bat sample collection and molecular CoV screening to fill in gaps in our previous sampling and fully characterize natural SARSr-CoV diversity in southern China. We will sequence receptor binding domains (spike proteins) to identify viruses with the highest potential for spillover which we will include in our experimental investigations (Aim 3). Aim 2. Community, and clinic-based syndromic, surveillance to capture SARSr-CoV spillover, routes of exposure and potential public health consequences. We will conduct biological-behavioral surveillance in high-risk populations, with known bat contact, in community and clinical settings to 1) identify risk factors for serological and PCR evidence of bat SARSr-CoVs; & 2) assess possible health effects of SARSr-CoVs infection in people. We will analyze bat-CoV serology against human-wildlife contact and exposure data to quantify risk factors and health impacts of SARSr-CoV spillover. Aim 3. In vitro and in vivo characterization of SARSr-CoV spillover risk, coupled with spatial and phylogenetic analyses to identify the regions and viruses of public health concern. We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential. We will combine these data with bat host distribution, viral diversity and phylogeny, human survey of risk behaviors and illness, and serology to identify SARSr-CoV spillover risk hotspots across southern China. Together these data and analyses will be critical for the future development of public health interventions and enhanced surveillance to prevent the re-emergence of SARS or the emergence of a novel SARSr-CoV.

https://taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R01AI110964&arg_ProgOfficeCode=104

>A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

https://pubmed.ncbi.nlm.nih.gov/26269185/

>>62774

>>62776

>>62767

>Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission.

Importance: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

https://pubmed.ncbi.nlm.nih.gov/26269185/

>>62774

>>62776

>>62767

>Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission.

Importance: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

https://pubmed.ncbi.nlm.nih.gov/26269185/

>>62774

>>62776

>>62767

>Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission.

Importance: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

https://pubmed.ncbi.nlm.nih.gov/26269185/

>infectious clone technology

with their spike proteins fanny packs

kek

damn fauci is paul riser in aliens, trying to bring the organism back for the company

>>62752

>humanized mice.

Humanized mouse is a general term that refers to a mouse that has been engrafted with something from a human. This could be a short strand of human DNA, human tissue, a human tumor, a humanized immune system, or parts of the human microbiome.

Why humanized mice? - The Jackson Laboratory

www.jax.org/news-and-insights/jax-blog/2020/july/why-humanized-mice

>>62783

>>62783

did faushi get his feelings hurt?

Fauci and co were the

DEVELOPERS

DEVELOPERS

DEVELOPERS

of covid-19

>>62783

>>62783

>>62783

>>62752

>>62752