SARS-CoV-2 originated from SARS-CoV-1-related Bat-CoVs through Pan-CoVs rather than from SARS-CoV-2-related Bat-CoVs

2021 ◽  
Author(s):  
Perumal Arumugam Desingu ◽  
K. Nagarajan
Keyword(s):  
New Host ◽  

AbstractThe emergence of the novel SARS-CoV-2 in 2019 sparked a dispute concerning its origin. Here, we report that the SARS-CoV-2 originated through pangolin-coronavirus (Pan-CoVs) from the SARS-CoV-related-bat-coronaviruses (SARS-CoV-1-rB-CoVs) rather than from SARS-CoV-2-related-bat-coronaviruses (SARS-CoV-2-rB-CoVs), in contrast to the previous thought. Further, our analyses strongly suggest that the Pan-CoVs evolved from the SARS-CoV-1-rB-CoVs without recombination. Further, our results suggest that the SARS-CoV-1-rB-CoVs’ perhaps jumped into the pangolin, which forced the viruses to mutate and adapt to the new host, and resulted in the origin of Pan-CoVs. Surprisingly, the Pan-CoVs formed an evolutionary intermediate between SARS-CoV-2 and SARS-CoV-2-rB-CoVs at the spike gene. Our findings also suggest that the Pan-CoV/GX and Pan-CoV/Guangdong lineages recombined to form the SARS-CoV-2 spike gene. We also found evidence that the SARS-CoV-2-rB-CoVs spike gene evolved via recombination between Pan-CoV/Guangdong and SARS-CoV-1-rB-CoVs. Overall, our findings suggest that the SARS-CoV-2 emerged from SARS-CoV-1-rB-CoVs through host jumping.

Parasitology ◽  
2010 ◽  
Vol 137 (10) ◽  
pp. 1487-1491 ◽  
Author(s):  
JENNIFER CAMPBELL ◽  
BETH KESSLER ◽  
CHRISTOPHER MAYACK ◽  
DHRUBA NAUG

SUMMARYInfection by a parasite often induces behavioural changes in the host and these changes may benefit either the host or the parasite. However, whether these changes are active host defence mechanisms or parasitic manipulations or simply incidental byproducts of the infection is not always clear. It has been suggested that understanding the proximate mechanisms of these changes as well as comparative studies could help distinguish these alternatives better. Behavioural fever is a common response to an infection in many animals and we investigated the phenomenon in the novel host-parasite relationship between the honeybee and the temperature-sensitive microsporidian Nosema ceranae. Our results show that infected bees prefer higher temperatures and even though this seems to benefit the pathogen, the proximate mechanism underlying this change is the pathological stress underlying the infection. Especially because it is a new host-parasite relationship, it is best to label the observed behavioural change as a case of incidental benefit although this does not rule out selection acting on it. We discuss the importance of looking at the behavioural outcomes of host-parasite relationships and the importance of studying them at multiple levels for understanding their origin and maintenance.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ritu Mishra ◽  
Akhil C. Banerjea

SARS-CoV-2, the novel coronavirus infection has consistently shown an association with neurological anomalies in patients, in addition to its usual respiratory distress syndrome. Multi-organ dysfunctions including neurological sequelae during COVID-19 persist even after declining viral load. We propose that SARS-CoV-2 gene product, Spike, is able to modify the host exosomal cargo, which gets transported to distant uninfected tissues and organs and can initiate a catastrophic immune cascade within Central Nervous System (CNS). SARS-CoV-2 Spike transfected cells release a significant amount of exosomes loaded with microRNAs such as miR-148a and miR-590. microRNAs gets internalized by human microglia and suppress target gene expression of USP33 (Ubiquitin Specific peptidase 33) and downstream IRF9 levels. Cellular levels of USP33 regulate the turnover time of IRF9 via deubiquitylation. Our results also demonstrate that absorption of modified exosomes effectively regulate the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-β. These results uncover a bystander pathway of SARS-CoV-2 mediated CNS damage through hyperactivation of human microglia. Our results also attempt to explain the extra-pulmonary dysfunctions observed in COVID-19 cases when active replication of virus is not supported. Since Spike gene and mRNAs have been extensively picked up for vaccine development; the knowledge of host immune response against spike gene and protein holds a great significance. Our study therefore provides novel and relevant insights regarding the impact of Spike gene on shuttling of host microRNAs via exosomes to trigger the neuroinflammation.


2018 ◽  
Vol 86 (3) ◽  
Author(s):  
Molly Staley ◽  
Geoffrey E. Hill ◽  
Chloe C. Josefson ◽  
Jonathan W. Armbruster ◽  
Camille Bonneaud

ABSTRACTWhile direct contact may sometimes be sufficient to allow a pathogen to jump into a new host species, in other cases, fortuitously adaptive mutations that arise in the original donor host are also necessary. Viruses have been the focus of most host shift studies, so less is known about the importance of ecological versus evolutionary processes to successful bacterial host shifts. Here we tested whether direct contact with the novel host was sufficient to enable the mid-1990s jump of the bacteriumMycoplasma gallisepticumfrom domestic poultry to house finches (Haemorhous mexicanus). We experimentally inoculated house finches with two genetically distinctM. gallisepticumstrains obtained either from poultry (Rlow) or from house finches (HF1995) during an epizootic outbreak. All 15 house finches inoculated with HF1995 became infected, whereas Rlow successfully infected 12 of 15 (80%) inoculated house finches. Comparisons among infected birds showed that, relative to HF1995, Rlow achieved substantially lower bacterial loads in the host respiratory mucosa and was cleared faster. Furthermore, Rlow-infected finches were less likely to develop clinical symptoms than HF1995-infected birds and, when they did, displayed milder conjunctivitis. The lower infection success of Rlow relative to HF1995 was not, however, due to a heightened host antibody response to Rlow. Taken together, our results indicate that contact between infected poultry and house finches was not, by itself, sufficient to explain the jump ofM. gallisepticumto house finches. Instead, mutations arising in the original poultry host would have been necessary for successful pathogen emergence in the novel finch host.


2016 ◽  
Vol 12 (10) ◽  
pp. 20160553 ◽  
Author(s):  
Ruth Pye ◽  
Rodrigo Hamede ◽  
Hannah V. Siddle ◽  
Alison Caldwell ◽  
Graeme W. Knowles ◽  
...  

Devil facial tumour disease (DFTD) is a recently emerged fatal transmissible cancer decimating the wild population of Tasmanian devils ( Sarcophilus harrisii ). Biting transmits the cancer cells and the tumour develops in the new host as an allograft. The literature reports that immune escape mechanisms employed by DFTD inevitably result in host death. Here we present the first evidence that DFTD regression can occur and that wild devils can mount an immune response against the disease. Of the 52 devils tested, six had serum antibodies against DFTD cells and, in one case, prominent T lymphocyte infiltration in its tumour. Notably, four of the six devils with serum antibody had histories of DFTD regression. The novel demonstration of an immune response against DFTD in wild Tasmanian devils suggests that a proportion of wild devils can produce a protective immune response against naturally acquired DFTD. This has implications for tumour–host coevolution and vaccine development.


2020 ◽  
Author(s):  
ZHONGNENG XU

The mechanisms of some infection events of the novel coronavirus (SARS-CoV-2) remain unknown, and new ideas of the transmission modes are needed. The present study proposed that the infectiousness of RNAs was one of the transmission routes of SARS-CoV-2. Possible explanations included RNAs controlling replication and metabolic processes of SARS-CoV-2, the estimated stabilization time of RNAs in the air being enough for them to encounter a new host, the infectious disease transmitted by free RNAs having been reported, etc. If additional detection results show that the proportion of RNA in the environment is higher than the proportion of RNA in the novel coronavirus particles, it suggests the potential presence of free RNA genomes of SARS-CoV-2 in the environment. Spatial array methods to detect the spatial distribution of RNAs should be applicated to assess the risk of viral infection within crowded places. It is worthwhile to compare the effects of SARS-CoV-2 components (e.g., virus particles, positive RNA strands, negative RNA strands, and virus proteins) on symptoms to study the mechanism of asymptomatic infection. More stringent protective measures based on the infectiousness of RNAs were provided. For the medical purpose, studying environmental RNAs (eRNAs) is important. I believe that further investigation of the infection capabilities of viral RNAs will yield useful information.


Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 125 ◽  
Author(s):  
Theocharis Tsoleridis ◽  
Joseph Chappell ◽  
Okechukwu Onianwa ◽  
Denise Marston ◽  
Anthony Fooks ◽  
...  

The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.


2020 ◽  
Vol 22 (1) ◽  
pp. 80
Author(s):  
Massimiliano S. Tagliamonte ◽  
Nabil Abid ◽  
Stefano Borocci ◽  
Elisa Sangiovanni ◽  
David A. Ostrov ◽  
...  

Our evolutionary and structural analyses revealed that the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) spike gene is a complex mosaic resulting from several recombination events. Additionally, the fixation of variants has mainly been driven by purifying selection, suggesting the presence of conserved structural features. Our dynamic simulations identified two main long-range covariant dynamic movements of the novel glycoprotein, and showed that, as a result of the evolutionary duality, they are preserved. The first movement involves the receptor binding domain with the N-terminal domain and the C-terminal domain 2 and is maintained across human, bat and pangolin coronaviruses. The second is a complex network of long-range dynamics specific to SARS-CoV-2 involving the novel PRRA and the conserved KR*SF cleavage sites, as well as conserved segments in C-terminal domain 3. These movements, essential for host cell binding, are maintained by hinges conserved across human, bat, and pangolin coronaviruses glycoproteins. The hinges, located around Threonine 333 and Proline 527 within the N-terminal domain and C-terminal domain 2, represent candidate targets for the future development of novel pan-coronavirus inhibitors. In summary, we show that while recombination created a new configuration that increased the covariant dynamic movements of the SARS-CoV-2 glycoprotein, negative selection preserved its inter-domain structure throughout evolution in different hosts and inter-species transmissions.


2010 ◽  
Vol 34 (8) ◽  
pp. S33-S33
Author(s):  
Wenchao Ou ◽  
Haifeng Chen ◽  
Yun Zhong ◽  
Benrong Liu ◽  
Keji Chen

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