The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

Science, Год журнала: 2022, Номер 377(6609), С. 960 - 966

Опубликована: Июль 26, 2022

Understanding the circumstances that lead to pandemics is important for their prevention. We analyzed genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in disease 2019 (COVID-19) pandemic. show SARS-CoV-2 before February 2020 likely comprised only two distinct viral lineages, denoted "A" and "B." Phylodynamic rooting methods, coupled with epidemic simulations, reveal these lineages were result at least separate cross-species transmission events into humans. The first zoonotic involved lineage B viruses around 18 November (23 October 8 December), introduction A occurred within weeks this event. These findings indicate it unlikely circulated widely humans define narrow window between when jumped cases COVID-19 reported. As other coronaviruses, emergence resulted from multiple events.

Язык: Английский

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Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 26, 2022

Abstract The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns variants include possible recombinants, as genome recombination an important evolutionary mechanism for the emergence and re-emergence human viral pathogens. In this study, we identified diverse events between two major subvariants (BA.1 BA.2) other concern (VOCs) interest (VOIs), suggesting that co-infection subsequent play roles in ongoing evolution SARS-CoV-2. Through scanning high-quality completed spike gene sequences, 18 core mutations BA.1 (frequency >99%) 27 BA.2 (nine than BA.1) were identified, which 15 are specific to Omicron. share nine common amino acid (three protein with most VOCs, a origin from these VOCs. There three Alpha-related BA.2, phylogenetically closer Alpha Revertant found some dominant >95%) BA.1. Most notably, multiple characteristic Delta have been also “Deltacron”-like Variants isolated since November 11, 2021 South Africa, implies occurring Monitoring evolving SARS-CoV-2 genomes especially critically recognition abrupt changes attributes including its epitopes may call vaccine modifications.

Язык: Английский

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Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission

Nature Microbiology, Год журнала: 2022, Номер 7(12), С. 2011 - 2024

Опубликована: Ноя. 10, 2022

Wildlife reservoirs of broad-host-range viruses have the potential to enable evolution viral variants that can emerge infect humans. In North America, there is phylogenomic evidence continual transmission severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans white-tailed deer (Odocoileus virginianus) through unknown means, but no We carried out an observational surveillance study in Ontario, Canada during November and December 2021 (n = 300 deer) identified a highly divergent lineage SARS-CoV-2 (B.1.641). This one most lineages so far, with 76 mutations (including 37 previously associated non-human mammalian hosts). From set five complete two partial deer-derived genomes we applied phylogenomic, recombination, selection mutation spectrum analyses, which provided for shared ancestry mink-derived virus. Our analysis also revealed epidemiologically linked human infection. Taken together, our findings provide sustained deer-to-human transmission.

Язык: Английский

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Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Май 27, 2022

Abstract SARS-CoV-2, the causative agent of COVID-19 pandemic, can infect a wide range mammals. Since its spread in humans, secondary host jumps SARS-CoV-2 from humans to multiple domestic and wild populations mammals have been documented. Understanding extent adaptation these animal hosts is critical for assessing threat that spillback animal-adapted into poses. We compare genomic landscapes isolated species profiling mutational biases indicative potentially different selective pressures animals. focus on viral genomes mink ( Neovison vison ) white-tailed deer Odocoileus virginianus which independent outbreaks driven by onward animal-to-animal transmission reported. identify five candidate mutations animal-specific (NSP9_G37E, Spike_F486L, Spike_N501T, Spike_Y453F, ORF3a_L219V), one (NSP3a_L1035F), though they appear confer minimal advantage human-to-human transmission. No considerable changes mutation rate or evolutionary trajectory has resulted circulation thus far. Our findings suggest was required following human-to-animal spillover, highlighting ‘generalist’ nature as mammalian pathogen.

Язык: Английский

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Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function

Molecular Biology and Evolution, Год журнала: 2022, Номер 39(4)

Опубликована: Март 16, 2022

Among the 30 nonsynonymous nucleotide substitutions in Omicron S-gene are 13 that have only rarely been seen other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of at sites will likely impact (1) interactions between subunits Spike trimer and predisposition to shift from down up configurations, (2) with ACE2 receptors, (3) priming for membrane fusion. We show here that, based on both rarity these intrapatient sequencing reads patterns selection codon where occur related sarbecoviruses, prior emergence would predicted decrease fitness any virus which they occurred. further propose each clusters therefore cooperatively interact mitigate their individual costs, and, combination mutations, adaptively alter function Spike. Given evident epidemic growth advantages overall previously known lineages, it is crucial determine how such complex highly adaptive mutation constellations were assembled S-gene, why, despite unprecedented global genomic surveillance efforts, early stages this assembly process went completely undetected.

Язык: Английский

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Pandemic origins and a One Health approach to preparedness and prevention: Solutions based on SARS-CoV-2 and other RNA viruses

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(42)

Опубликована: Окт. 10, 2022

COVID-19 is the latest zoonotic RNA virus epidemic of concern. Learning how it began and spread will help to determine reduce risk future events. We review major outbreaks since 1967 identify common features opportunities prevent emergence, including ancestral viral origins in birds, bats, other mammals; animal reservoirs intermediate hosts; pathways for spillover community spread, leading local, regional, or international outbreaks. The increasing scientific evidence concerning Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) most consistent with a origin pathway from wildlife people via farming trade. apply what we know about these relevant, feasible, implementable interventions. three primary targets pandemic prevention preparedness: first, smart surveillance coupled epidemiological assessment across wildlife–livestock–human (One Health) interfaces; second, research enhance preparedness expedite development vaccines therapeutics; third, strategies underlying drivers influence misinformation. For all three, continued efforts improve integrate biosafety biosecurity implementation One Health approach are essential. discuss new models address challenges creating an inclusive effective governance structure, necessary stable funding cross-disciplinary collaborative research. Finally, offer recommendations feasible actions close knowledge gaps continuum response future.

Язык: Английский

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From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer

PLoS Pathogens, Год журнала: 2022, Номер 18(3), С. e1010197 - e1010197

Опубликована: Март 21, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19) in humans, has a broad host range, and is able to infect domestic wild animal species. Notably, white-tailed deer (WTD, Odocoileus virginianus ), most widely distributed cervid species Americas, were shown be highly susceptible SARS-CoV-2 challenge studies reported natural infection/exposure rates approaching 30–40% free-ranging WTD U.S. Thus, understanding infection transmission dynamics critical prevent future zoonotic at human-WTD interface during hunting or venison farming, for implementation effective control measures. Here, we demonstrated that following intranasal inoculation with B.1 lineage, fawns (~8-month-old) shed infectious virus up day 5 post-inoculation (pi), high viral loads nasal oral secretions. This resulted efficient deer-to-deer on 3 pi. Consistent lack shedding after pi, no was observed contact animals added days 6 9 We have also investigated tropism sites replication adult (3–4 years age). Infectious detected pi secretions, from various respiratory-, lymphoid-, central nervous system tissues, indicating tissue multiple replication. The study provides important insights WTD, potential become reservoir field.

Язык: Английский

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A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июль 27, 2022

Abstract We report a live-attenuated SARS-CoV-2 vaccine candidate with (i) re-engineered viral transcription regulator sequences and (ii) deleted open-reading-frames (ORF) 3, 6, 7, 8 (∆3678). The ∆3678 virus replicates about 7,500-fold lower than wild-type on primary human airway cultures, but restores its replication interferon-deficient Vero-E6 cells that are approved for production. is highly attenuated in both hamster K18-hACE2 mouse models. A single-dose immunization of the protects hamsters from challenge transmission. Among ORFs virus, ORF3a accounts most attenuation through antagonizing STAT1 phosphorylation during type-I interferon signaling. also developed an mNeonGreen reporter high-throughput neutralization antiviral testing. Altogether, results suggest may serve as research tool potential biosafety level-2 use.

Язык: Английский

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White-tailed deer ( Odocoileus virginianus ) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(6)

Опубликована: Янв. 31, 2023

The spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to white-tailed deer (WTD) and its ability transmit raised concerns about the role WTD in epidemiology ecology virus. Here, we present a comprehensive cross-sectional study assessing prevalence, genetic diversity, evolution SARS-CoV-2 State New York (NY). A total 5,462 retropharyngeal lymph node samples collected free-ranging hunter-harvested during hunting seasons 2020 (Season 1, September December 2020, n = 2,700) 2021 2, 2021, 2,762) were tested by real-time RT–PCR (rRT-PCR). RNA was detected 17 (0.6%) Season 1 583 (21.1%) 2. Hotspots infection identified multiple confined geographic areas NY. Sequence analysis genomes 164 demonstrated presence lineages cocirculation three major variants concern (VOCs) (Alpha, Gamma, Delta) WTD. Our suggests occurrence events (human deer) Alpha Delta with subsequent deer-to-deer transmission adaptation viruses. Detection Gamma long after their broad circulation NY that may serve as wildlife reservoir for VOCs no longer circulating humans. Thus, implementation continuous surveillance programs monitor dynamics is warranted, measures minimize virus between animals are urgently needed.

Язык: Английский

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Transmission of SARS-CoV-2 in free-ranging white-tailed deer in the United States

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 10, 2023

Abstract SARS-CoV-2 is a zoonotic virus with documented bi-directional transmission between people and animals. Transmission of from humans to free-ranging white-tailed deer ( Odocoileus virginianus ) poses unique public health risk due the potential for reservoir establishment where variants may persist evolve. We collected 8,830 respiratory samples across Washington, D.C. 26 states in United States November 2021 April 2022. obtained 391 sequences identified 34 Pango lineages including Alpha, Gamma, Delta, Omicron variants. Evolutionary analyses showed these viruses originated at least 109 independent spillovers humans, which resulted 39 cases subsequent local deer-to-deer three spillover back humans. Viruses repeatedly adapted recurring amino acid substitutions spike other proteins. Overall, our findings suggest that multiple were introduced, became enzootic, co-circulated deer.

Язык: Английский

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