Jumping species—a mechanism for coronavirus persistence and survival

Menachery, Vineet D.; Graham, Rachel L.; Baric, Ralph S.

doi:10.1016/j.coviro.2017.01.002

Cited by 124 publications

(130 citation statements)

References 53 publications

(71 reference statements)

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“…Successful cross-species transmission depends foremost on the virus' ability to bind and functionally use a receptor within an alternative host, causing the S protein to be the driver of CoV emergence. However, (changes in) non-S genes may codetermine virus emergence in novel hosts (63). Our data indicate that PDCoV has access to cells of an exceptionally diverse range of species by binding to an interspecies conserved domain on APN.…”

Section: S1 (B) -Mfc (µM)mentioning

confidence: 84%

Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility

Hulswit

Kenney

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

208

274

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Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.

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Section: S1 (B) -Mfc (µM)mentioning

confidence: 84%

Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility

Hulswit

Kenney

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

208

274

View full text Add to dashboard Cite

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“…Coronaviruses (CoVs) are enveloped positive-sense RNA viruses that belong to the family Coronaviridae. They have been found in a wide variety of animals and can cause respiratory, enteric, hepatic and neurological diseases [1,2].…”

Section: Abstract Viral Metagenomics · Coronavirus · Infectious Broncmentioning

confidence: 99%

A recombinant infectious bronchitis virus from a chicken with a spike gene closely related to that of a turkey coronavirus

Wang

Cui

et al. 2020

Arch Virol

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Using viral metagenomics, the complete genome sequence of an infectious bronchitis virus (IBV) strain (named ahysx-1) from a fecal sample from a healthy chicken in Anhui province, China, was determined. The genome sequence of ahysx-1 was found to be very similar to that of IBV strain ck/CH/LLN/131040 (KX252787), except for the spike gene region, which is similar to that of a turkey coronavirus strain (EU022526), suggesting that ahysx-1 is a recombinant. Recombination analysis and phylogenetic analysis based on the genomic sequences of ahysx-1 and other related strains confirmed that ahysx-1 appears to be a recombinant resulting from a recombination event that occurred between a chicken coronavirus and a turkey coronavirus. Further studies need to be performed to determine whether this recombinant IBV strain is pathogenic and whether it is transmitted between chickens and turkeys. Keywords Viral metagenomics · Coronavirus · Infectious bronchitis virus · Genome recombinationCoronaviruses (CoVs) are enveloped positive-sense RNA viruses that belong to the family Coronaviridae. They have been found in a wide variety of animals and can cause respiratory, enteric, hepatic and neurological diseases [1,2].

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“…still occurring 6 years after its initial discovery (3). Coupled with recently discovered SARS-and MERS-like coronaviruses circulating in animal populations, the threat of a coronavirus fueled outbreak remains far from remote (4). With this in mind, strategies must be developed to rapidly respond to a potential CoV emergence or reemergence event.…”

mentioning

confidence: 99%

Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines

Menachery

Gralinski

Mitchell

et al. 2018

J Virol

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With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2=O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the severe acute respiratory syndrome-CoV mouse model, an NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2=O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2=O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live attenuated coronavirus vaccines. IMPORTANCE Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations such as the aged and immunocompromised. This study illustrates that despite success in young models, the 2=O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a standalone vaccine strategy. Importantly, the 2=O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2=O methyltransferase attenuation as a major component of future live attenuated coronavirus vaccines.

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Jumping species—a mechanism for coronavirus persistence and survival

Cited by 124 publications

References 53 publications

Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility

Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility

A recombinant infectious bronchitis virus from a chicken with a spike gene closely related to that of a turkey coronavirus

Combination Attenuation Offers Strategy for Live Attenuated Coronavirus Vaccines

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