The zoonotic origins of seasonal human coronaviruses

In a recent study published in bioRxiv* Prepress server, researchers analyzed the evolution and origin of seasonal human coronaviruses (sHCoVs).

Study: Origins and evolution of seasonal human coronaviruses. Image Credit: Corona Borealis Studio / Shutterstock

background

Four of the HCoVs, NL63, 229E, HKU1, and OC43 are endemic worldwide, and represent five to 30% of human respiratory diseases. Coronavirus infection primarily affects the gastrointestinal tract and upper respiratory tract, often resulting in mild respiratory infections. However, CoVs can lead to life-threatening pneumonia and bronchiolitis in young children, newborns, the elderly, and immunocompromised persons.

While sHCoVs are found globally and have a typical seasonality that extends from December to April, their detection rate varies depending on time and location. Furthermore, the evolution and epidemiology of these cardiac viruses has not been explored relative to other seasonal respiratory viruses such as influenza and respiratory syncytial virus (RSV). This was due to their association with mild symptoms. Furthermore, there are no approved vaccines or drugs against the emerging coronavirus, and management consists of supportive measures.

Summarized within and between host/species recombination patterns identified by RDP4, for alphaCoVs (A) and betaCoVs (B).  For each type of novel coronavirus, virus recombination is shown;  Non-human and sHCoV (black arrows), within sHCoV species (blue arrows), and among sHCoV species (green arrows).  In orange, there is a single human coronavirus (FJ415324) that clusters with hoof and canine CoVs.  The figure was created with Biorender.

Summarized within and between host/species recombination patterns identified by RDP4, for alphaCoVs (A) and betaCoVs (B). For each type of novel coronavirus, virus recombination is shown; Non-human and sHCoV (black arrows), within sHCoV species (blue arrows), and among sHCoV species (green arrows). In orange, there is a single human coronavirus (FJ415324) that clusters with hoof and canine CoVs. The figure was created with Biorender.

about studying

In the present work, the researchers used a polygenic and whole-genome analysis technique to assess the evolutionary background of sHCoVs (NL63, 229E, HKU1, and OC43).

Using a set of 855 sequences obtained from GenBank, the team explored the evolutionary history of sHCoVs. They investigated animal origins, time of emergence, genetic diversity, rates and patterns of recombination, and adaptive protein modifications. The scientists used a polygenic analytical strategy to learn about the evolutionary background of nucleocapsid open reading frames, spikes, envelopes, and membranes (ORFs).

Researchers have generated maximum clade credibility (MCC) trees using whole genome sequencing (WGS) and envelope, spike, nucleocapsid, and membrane ORFs to study the zoonotic origins of the four coronavirus species. They calculated the apparent recombination frequencies between CoVs and across the genome using the software ClonalFrameML.

Illustration of the sHCoV genomes, not widely plotted.  ORFs were analyzed in orange in this study.

Illustration of the sHCoV genomes, not widely plotted. ORFs were analyzed in orange in this study.

Results and discussions

The team discovered that the evolutionary timescales of sHCoVs were more complex than previously thought due to the common recombination of CoVs, which consist of between and within sHCoVs that occur at different rates. OC43 and 229E had the highest recombination rates within sHCoV, and β-CoVs had the highest intra-genus recombination rate. Moreover, in HKU1, NL63 and α-CoVs, the substitutions for each recombination incident were conversely greater.

The authors stated that the origins of the sHCoVs OC43 and 229E may depend on the gene evaluated. OC43 could be ancestral to dogs, ungulates or rabbits, while 229E could come from a camel, bat, or an unknown intermediate host, depending on the gene examined.

Maximum validity of the clade (MCC) was inferred from the D5 dataset for whole genome (WGS), spike, nucleocapsid, membrane and envelope proteins, with branches color-coded by the inferred coronavirus host.  The upper panel shows MCC trees from alphacoronaviruses while the lower panel shows MCC trees from betacoronaviruses.  Corona virus interfaces for humans, camels and pigs have collapsed to increase readability.  Human* is a single human coronavirus (FJ415324) that aggregates with hoofed and canine CoVs.

Maximum validity of the clade (MCC) was inferred from the D5 dataset for whole genome (WGS), spike, nucleocapsid, membrane and envelope proteins, with branches color-coded by the inferred coronavirus host. The upper panel shows MCC trees from alphacoronaviruses while the lower panel shows MCC trees from betacoronaviruses. Corona virus interfaces for humans, camels and pigs have collapsed to increase readability. Human* is a single human coronavirus (FJ415324) that aggregates with hoofed and canine CoVs.

The current analysis did not significantly support the origin of 229E from camels. Conversely, independent transmission of coronaviruses from bats to humans and camels appears to have been more likely. Current observations extend the list of putative OC43 origin or intermediate hosts to include other rabbits, ungulates and canines, both wild and domesticated but always close to humans.

Scientists hypothesized that two independent non-human-to-human accidents could occur in HKU1. HKU1 harbored the oldest and most recent common ancestor, consisting of two genetically different genotypes (B and A), presumably indicating two separate transmission episodes of murine CoVs. Besides, genotype B had greater genetic diversity than other sHCoVs.

The team discovered that the sHCoVs were non-human recombinants of CoVs, meaning that either the sHCoVs that appeared in humans were actually recombinants of many non-human CoVs or that the current sHCoVs are the result of back-and-forth transmission of the virus between humans and non-humans. human hosts. The authors describe previously unknown recombination between sHCoV species between the same genera and recombination within 229E. The present results show that recombination often occurs outside of the spike protein, which has often been the subject of recombination studies.

Finally, although the non-human branches of sHCoV do not always appear to be among the positive selection, the authors detected common amino acid (AA) changes in several proteins in these branches.

Conclusions

To summarize, the authors discovered that the origins of sHCoVs were more complex and mysterious than previously thought, indicative of an evolutionary reconstruction that suggests that many ORFs within sHCoVs may have unique sources. In addition, they note that recombination and reduction, particularly among non-human hosts, may play a role in the unknown and complex evolutionary pathways of sHCoVs. Additional sequence data and re-analysis will also help to gain a better understanding of the evolutionary history of sHCoV.

According to the researchers, continuous monitoring of CoVs in all non-human hosts may help assess the complex evolution of CoVs and their regular host transformations. Tracking the evolution of the novel coronavirus has implications for vaccine, diagnosis, and treatment development, better knowledge of their evolutionary past, and pathways for the potential emergence of novel human coronaviruses.

*Important note

bioRxiv It publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behaviour, or be treated as established information.

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