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1.
PLoS Pathog ; 17(11): e1010053, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34748603

RESUMO

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as "Cluster 5" that contained mutations in the spike protein. However, the functional properties of these "Cluster 5" mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/epidemiologia , Adaptação ao Hospedeiro , Vison/imunologia , Mutação , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/genética , Animais , Sítios de Ligação , COVID-19/imunologia , COVID-19/terapia , COVID-19/transmissão , COVID-19/virologia , Feminino , Humanos , Imunização Passiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Vison/virologia , Simulação de Dinâmica Molecular , Países Baixos/epidemiologia , Ligação Proteica , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Adulto Jovem
2.
Viruses ; 13(10)2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34696445

RESUMO

In summer 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was detected on mink farms in Utah. An interagency One Health response was initiated to assess the extent of the outbreak and included sampling animals from on or near affected mink farms and testing them for SARS-CoV-2 and non-SARS coronaviruses. Among the 365 animals sampled, including domestic cats, mink, rodents, raccoons, and skunks, 261 (72%) of the animals harbored at least one coronavirus. Among the samples that could be further characterized, 127 alphacoronaviruses and 88 betacoronaviruses (including 74 detections of SARS-CoV-2 in mink) were identified. Moreover, at least 10% (n = 27) of the coronavirus-positive animals were found to be co-infected with more than one coronavirus. Our findings indicate an unexpectedly high prevalence of coronavirus among the domestic and wild free-roaming animals tested on mink farms. These results raise the possibility that mink farms could be potential hot spots for future trans-species viral spillover and the emergence of new pandemic coronaviruses.


Assuntos
Alphacoronavirus/isolamento & purificação , COVID-19/epidemiologia , COVID-19/veterinária , SARS-CoV-2/isolamento & purificação , Alphacoronavirus/classificação , Alphacoronavirus/genética , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Gatos , Hotspot de Doença , Feminino , Masculino , Mephitidae/virologia , Camundongos , Vison/virologia , Guaxinins/virologia , SARS-CoV-2/classificação , SARS-CoV-2/genética , Utah/epidemiologia
3.
PLoS Pathog ; 17(9): e1009883, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492088

RESUMO

SARS-CoV-2 infection outbreaks in minks have serious implications associated with animal health and welfare, and public health. In two naturally infected mink farms (A and B) located in Greece, we investigated the outbreaks and assessed parameters associated with virus transmission, immunity, pathology, and environmental contamination. Symptoms ranged from anorexia and mild depression to respiratory signs of varying intensity. Although the farms were at different breeding stages, mortality was similarly high (8.4% and 10.0%). The viral strains belonged to lineages B.1.1.218 and B.1.1.305, possessing the mink-specific S-Y453F substitution. Lung histopathology identified necrosis of smooth muscle and connective tissue elements of vascular walls, and vasculitis as the main early key events of the acute SARS-CoV-2-induced broncho-interstitial pneumonia. Molecular investigation in two dead minks indicated a consistently higher (0.3-1.3 log10 RNA copies/g) viral load in organs of the male mink compared to the female. In farm A, the infected farmers were responsible for the significant initial infection of 229 out of 1,000 handled minks, suggesting a very efficient human-to-mink transmission. Subsequent infections across the sheds wherein animals were being housed occurred due to airborne transmission. Based on a R0 of 2.90 and a growth rate equal to 0.293, the generation time was estimated to be 3.6 days, indicative of the massive SARS-CoV-2 dispersal among minks. After the end of the outbreaks, a similar percentage of animals were immune in the two farms (93.0% and 93.3%), preventing further virus transmission whereas, viral RNA was detected in samples collected from shed surfaces and air. Consequently, strict biosecurity is imperative during the occurrence of clinical signs. Environmental viral load monitoring, in conjunction with NGS should be adopted in mink farm surveillance. The minimum proportion of minks that need to be immunized to avoid outbreaks in farms was calculated at 65.5%, which is important for future vaccination campaigns.


Assuntos
COVID-19/veterinária , Vison/virologia , Animais , COVID-19/epidemiologia , COVID-19/genética , COVID-19/transmissão , Surtos de Doenças/veterinária , Microbiologia Ambiental , Fazendas , Feminino , Grécia/epidemiologia , Humanos , Masculino , Vison/genética , Exposição Ocupacional , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
4.
Sci Rep ; 11(1): 17422, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465838

RESUMO

The SARS-CoV-2 pandemic has raised concerns in the identification of the hosts of the virus since the early stages of the outbreak. To address this problem, we proposed a deep learning method, DeepHoF, based on extracting viral genomic features automatically, to predict the host likelihood scores on five host types, including plant, germ, invertebrate, non-human vertebrate and human, for novel viruses. DeepHoF made up for the lack of an accurate tool, reaching a satisfactory AUC of 0.975 in the five-classification, and could make a reliable prediction for the novel viruses without close neighbors in phylogeny. Additionally, to fill the gap in the efficient inference of host species for SARS-CoV-2 using existing tools, we conducted a deep analysis on the host likelihood profile calculated by DeepHoF. Using the isolates sequenced in the earliest stage of the COVID-19 pandemic, we inferred that minks, bats, dogs and cats were potential hosts of SARS-CoV-2, while minks might be one of the most noteworthy hosts. Several genes of SARS-CoV-2 demonstrated their significance in determining the host range. Furthermore, a large-scale genome analysis, based on DeepHoF's computation for the later pandemic in 2020, disclosed the uniformity of host range among SARS-CoV-2 samples and the strong association of SARS-CoV-2 between humans and minks.


Assuntos
COVID-19/virologia , Gatos/virologia , Quirópteros/virologia , Cães/virologia , Vison/virologia , SARS-CoV-2/classificação , Algoritmos , Animais , COVID-19/transmissão , Aprendizado Profundo , Especificidade de Hospedeiro , Humanos , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Análise de Sequência de RNA
5.
Occup Environ Med ; 78(12): 893-899, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34330815

RESUMO

OBJECTIVE: Unprecedented SARS-CoV-2 infections in farmed minks raised immediate concerns regarding transmission to humans and initiated intensive environmental investigations to assess occupational and environmental exposure. METHODS: Air sampling was performed at infected Dutch mink farms, at farm premises and at nearby residential sites. A range of other environmental samples were collected from minks' housing units, including bedding materials. SARS-CoV-2 RNA was analysed in all samples by quantitative PCR. RESULTS: Inside the farms, considerable levels of SARS-CoV-2 RNA were found in airborne dust, especially in personal inhalable dust samples (approximately 1000-10 000 copies/m3). Most of the settling dust samples tested positive for SARS-CoV-2 RNA (82%, 75 of 92). SARS-CoV-2 RNA was not detected in outdoor air samples, except for those collected near the entrance of the most recently infected farm. Many samples of minks' housing units and surfaces contained SARS-CoV-2 RNA. CONCLUSIONS: Infected mink farms can be highly contaminated with SARS-CoV-2 RNA. This warns of occupational exposure, which was substantiated by considerable SARS-CoV-2 RNA concentrations in personal air samples. Dispersion of SARS-CoV-2 to outdoor air was found to be limited and SARS-CoV-2 RNA was not detected in air samples collected beyond farm premises, implying a negligible risk of environmental exposure to nearby communities. Our occupational and environmental risk assessment is in line with whole genome sequencing analyses showing mink-to-human transmission among farm workers, but no indications of direct zoonotic transmission events to nearby communities.


Assuntos
Poeira/análise , Exposição Ambiental , Fazendas , Vison/virologia , Exposição Ocupacional , RNA Viral/isolamento & purificação , SARS-CoV-2/isolamento & purificação , Animais , Humanos , Países Baixos/epidemiologia
6.
Viruses ; 13(6)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208484

RESUMO

Pets play a crucial role in the development of human feelings, social life, and care. However, in the era of the prevailing global pandemic of COVID-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many questions addressing the routes of the virus spread and transmission to humans are dramatically emerging. Although cases of SARS-CoV-2 infection have been found in pets including dogs, cats, and ferrets, to date there is no strong evidence for pet-to-human transmission or sustained pet-to-pet transmission of SARS-CoV-2. However, an increasing number of studies reporting detection of SARS-CoV-2 in farmed minks raises suspicion of potential viral transmission from these animals to humans. Furthermore, due to the high susceptibility of cats, ferrets, minks and hamsters to COVID-19 infection under natural and/or experimental conditions, these animals have been extensively explored as animal models to study the SARS-CoV-2 pathogenesis and transmission. In this review, we present the latest reports focusing on SARS-CoV-2 detection, isolation, and characterization in pets. Moreover, based on the current literature, we document studies aiming to broaden the knowledge about pathogenicity and transmissibility of SARS-CoV-2, and the development of viral therapeutics, drugs and vaccines. Lastly, considering the high rate of SARS-CoV-2 evolution and replication, we also suggest routes of protection against the virus.


Assuntos
COVID-19/transmissão , Animais de Estimação/virologia , SARS-CoV-2/patogenicidade , Zoonoses/transmissão , Zoonoses/virologia , Animais , COVID-19/prevenção & controle , Gatos/virologia , Cães/virologia , Fazendas , Furões/virologia , Humanos , Vison/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
7.
J Vet Diagn Invest ; 33(5): 939-942, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34109885

RESUMO

Large numbers of mink have been infected with SARS-CoV2 containing the spike protein Y453F mutation in Europe, causing zoonosis concerns. To evaluate the genetic characteristics of the U.S. and Canadian mink-derived SARS-CoV2 sequences, we analyzed all animal-derived (977) and all Canadian (19,529) and U.S. (173,277) SARS-CoV2 sequences deposited in GISAID from December 2019 to March 12, 2021, and identified 2 dominant novel variants, the N501T-G142D variant and N501T-G142D-F486L variant, in the U.S. mink-derived SARS-CoV2 sequences. These variants were not found in mink from Canada or other countries. The Y453F mutation was not identified in the mink-derived sequences in the United States and Canada. The N501T mutation occurred 2 mo earlier in humans than in mink in the United States, and the novel N501T-G142D and N501T-G142D-F486L variants were found in humans prior to mink. Our results suggest that the novel SARS-CoV2 variants may have evolved during human infection and were then transmitted to mink populations in the United States.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Animais , COVID-19/veterinária , Canadá/epidemiologia , Vison/virologia , Mutação , RNA Viral , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Estados Unidos/epidemiologia
8.
Science ; 373(6555)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34168071

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization.


Assuntos
SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , COVID-19/transmissão , COVID-19/veterinária , COVID-19/virologia , Microscopia Crioeletrônica , Adaptação ao Hospedeiro , Humanos , Evasão da Resposta Imune , Vison/virologia , Modelos Moleculares , Mutação , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Receptores de Coronavírus/metabolismo , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
9.
PLoS One ; 16(5): e0247626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34038423

RESUMO

SARS-CoV-2 infection in minks has become a serious problem, as the virus may mutate and reinfect humans; some countries have decided to cull minks. Here, the virus sequencing data in minks were analysed and compared to those of human-virus. Although the mink-virus maintained the characteristics of human-virus, some variants rapidly mutated, adapting to minks. Some mink-derived variants infected humans, which accounted for 40% of the total SARS-CoV-2 cases in the Netherlands. These variants appear to be less lethal and infective compared to those in humans. Variants that have mutated further among minks were not found in humans. Such mink-viruses might be suitable for vaccination for humans, such as in the case of the smallpox virus, which is less infective and toxic to humans.


Assuntos
COVID-19/patologia , Vison/virologia , RNA Viral/química , SARS-CoV-2/genética , Animais , COVID-19/epidemiologia , COVID-19/veterinária , COVID-19/virologia , Humanos , Mutação , Países Baixos/epidemiologia , Análise de Componente Principal , RNA Viral/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Análise de Sequência de RNA
10.
PLoS One ; 16(5): e0252022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34038467

RESUMO

Diarrhea in mink kits is a major cause of disease and mortality in the mink production. The etiology remains unknown in most outbreaks due to a lack of diagnostic assays. In the current study we present an RT-qPCR method to detect mink astrovirus in fecal samples from mink kits with diarrhea. All sampled animals were classified based on age and patoanatomical evaluation as having pre-weaning diarrhea, diarrhea in the growth period or as having no macroscopic signs of diarrhea. Fecal samples were analyzed for MiAstV with RT-qPCR, next generation sequencing and electron microscopy in parallel. Mink astrovirus was detected with RT-qPCR in 92 out of 203 samples. This detection was confirmed by next generation sequencing in a high proportion of samples (22/27), and by visualization of astrovirus particles with EM in some of the samples. Mink astrovirus was highly prevalent (68%) among kits in the outbreaks of pre-weaning diarrhea, in particular outbreaks from May, while less prevalent in outbreaks in June. Mink astrovirus was detected in outbreaks of diarrhea in the growth period, though in a much lesser extent than in the pre-weaning period. The role of mink astrovirus in the diarrhea disease complex of mink remain to be investigated, and for that purpose this sensitive and robust RT-qPCR can be a valuable tool in the future.


Assuntos
Infecções por Astroviridae/diagnóstico , Astroviridae/isolamento & purificação , Diarreia/diagnóstico , Vison/virologia , Animais , Astroviridae/patogenicidade , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Dinamarca , Diarreia/veterinária , Diarreia/virologia , Surtos de Doenças , Fazendas , Fezes/virologia , Humanos , Reação em Cadeia da Polimerase em Tempo Real
12.
Infect Genet Evol ; 93: 104897, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33971305

RESUMO

A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer.


Assuntos
Vison/virologia , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Sítios de Ligação , COVID-19/transmissão , COVID-19/veterinária , COVID-19/virologia , Canadá , Dinamarca , Humanos , Países Baixos , Filogenia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Estados Unidos
13.
Virus Genes ; 57(3): 266-275, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33950332

RESUMO

An outbreak of canine distemper in 2017 in mink breeding farms (Shandong province, China) caused severe pneumonia, hardened footpads, and death in more than 5000 vaccinated animals. Sequencing of the hemagglutinin and fusion protein genes from the WH2 canine distemper virus (CDV) strain we isolated from the infected minks were clustered into the recently isolated CDV Asia-1 genotype group. The WH2 strain was distinct from the current vaccine strains, containing a novel potential N-glycosylation site in its hemagglutinin protein. It also contained amino acid mutations in the fusion protein gene (I87N, T110P and L386I), and the T110P mutation results in N-glycosylation site silencing. WH2 was highly virulent in both unvaccinated and vaccinated animals in our pathogenesis experiments. Immunohistochemistry results revealed positive staining of different organs in unvaccinated and vaccinated animals. The serum in vitro neutralizing antibody titers for the vaccinated mink group and a dog were higher for the WH2 strain than those of the HNly150520B strain (isolated from a dog). These findings indicate that the current commercial vaccines provide incomplete protection against WH2 challenge infections. Thus, a new vaccine strain is urgently needed to protect against variant CDV strains.


Assuntos
Vírus da Cinomose Canina/isolamento & purificação , Cinomose/virologia , Vison/virologia , Vacinas Virais/efeitos adversos , Animais , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/farmacologia , Cinomose/genética , Vírus da Cinomose Canina/patogenicidade , Cães , Genótipo , Vison/genética , Filogenia , Vacinação/efeitos adversos , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/farmacologia
14.
Cell Rep ; 35(3): 109017, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33857422

RESUMO

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to farmed mink has been observed in Europe and the US. In the infected animals, viral variants arose that harbored mutations in the spike (S) protein, the target of neutralizing antibodies, and these variants were transmitted back to humans. This raised concerns that mink might become a constant source of human infection with SARS-CoV-2 variants associated with an increased threat to human health and resulted in mass culling of mink. Here, we report that mutations frequently found in the S proteins of SARS-CoV-2 from mink are mostly compatible with efficient entry into human cells and its inhibition by soluble angiotensin-converting enzyme 2 (ACE2). In contrast, mutation Y453F reduces neutralization by an antibody with emergency use authorization for coronavirus disease 2019 (COVID-19) therapy and sera/plasma from COVID-19 patients. These results suggest that antibody responses induced upon infection or certain antibodies used for treatment might offer insufficient protection against SARS-CoV-2 variants from mink.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19 , Vison , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Células A549 , Enzima de Conversão de Angiotensina 2/imunologia , Animais , COVID-19/genética , COVID-19/imunologia , Chlorocebus aethiops , Cricetinae , Humanos , Vison/imunologia , Vison/virologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
15.
Virus Genes ; 57(3): 258-265, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860418

RESUMO

Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and neurological symptoms. This paper presents cases of astrovirus infection in mink from continental Europe. RNA was isolated from the brains and intestines of animals showing symptoms typical of shaking mink syndrome (n = 6). RT-PCR was used to amplify astrovirus genetic material, and the reaction products were separated on a 1% agarose gel. The specificity of the reaction was confirmed by sequencing fragment coding RdRP protein (length of sequencing product 170 bp) from all samples. The presence of astrovirus RNA was detected in each of the samples tested. Sequencing and bioinformatic analysis indicated the presence of the same variant of the virus in all samples. Comparison of the variant with the sequences available in bioinformatics databases confirmed that the Polish isolates form a separate clade, closely related to Danish isolates. The dissimilarity of the Polish variant to those isolated in other countries ranged from 2.4% (in relation to Danish isolates) to 7.1% (in relation to Canadian isolates). Phylogenetic relationships between variants appear to be associated with the geographic distances between them. To our knowledge, this work describes the first results on the molecular epidemiology of MAstV in continental Europe. The detection of MAstV in Central Europe indicates the need for further research to broaden our understanding of the molecular epidemiology of MAstV in Europe.


Assuntos
Infecções por Astroviridae/genética , Astroviridae/genética , Vison/virologia , Filogenia , Animais , Astroviridae/isolamento & purificação , Astroviridae/patogenicidade , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Vison/genética
16.
Viruses ; 13(4)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916308

RESUMO

Mink refractory diarrhea is a seasonal disease that occurs in many mink farms in China. Mink circovirus (MiCV) has been recognized as the causative agent of the disease. The aim of the study was to develop a subunit vaccine against mink refractory diarrhea. A recombinant baculovirus strain expressing the capsid protein was constructed using the baculovirus expression vector system (BEVS). A subunit vaccine was developed based on the capsid protein with appropriate adjuvant. Then, a field trial was carried out in two districts in order to evaluate the efficiency of the subunit vaccine. The field trial indicated that in total, only 1.8% of the minks developed typical diarrhea in the vaccinated group compared with 74.5% in the control group. The vaccination could significantly reduce the infection rate of MiCV among the mink herds and could restrain the virus' shedding from feces. Furthermore, the vaccinated group had a higher average litter size in the following year compared to the control group. Collectively, the results indicated that the subunit vaccine based on the capsid protein can provide reliable protection against MiCV infection.


Assuntos
Anticorpos Antivirais/sangue , Baculoviridae/genética , Proteínas do Capsídeo/genética , Infecções por Circoviridae/prevenção & controle , Infecções por Circoviridae/veterinária , Circovirus/imunologia , Diarreia/prevenção & controle , Vison/virologia , Vacinas Virais/imunologia , Animais , Capsídeo/imunologia , Capsídeo/metabolismo , Proteínas do Capsídeo/imunologia , China , Infecções por Circoviridae/imunologia , Circovirus/genética , Diarreia/virologia , Feminino , Masculino , Vacinas de Subunidades/imunologia , Vacinas Virais/administração & dosagem
17.
Int J Infect Dis ; 106: 228-236, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33785459

RESUMO

BACKGROUND: In Marseille, France, following a first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in March-May 2020, a second epidemic phase occurred from June, involving 10 new variants. The Marseille-4 variant caused an epidemic that started in August and is still ongoing. METHODS: The 1038 SARS-CoV-2 whole genome sequences obtained in our laboratory by next-generation sequencing with Illumina technology were analysed using Nextclade and nextstrain/ncov pipelines and IQ-TREE. A Marseille-4-specific qPCR assay was implemented. Demographic and clinical features were compared between patients with the Marseille-4 variant and those with earlier strains. RESULTS: Marseille-4 harbours 13 hallmark mutations. One leads to an S477N substitution in the receptor binding domain of the spike protein targeted by current vaccines. Using a specific qPCR, it was observed that Marseille-4 caused 12-100% of SARS-CoV-2 infections in Marseille from September 2020, being involved in 2106 diagnoses. This variant was more frequently associated with hypoxemia than were clade 20A strains before May 2020. It caused a re-infection in 11 patients diagnosed with different SARS-CoV-2 strains before June 2020, suggesting either short-term protective immunity or a lack of cross-immunity. CONCLUSIONS: Marseille-4 should be considered as a major SARS-CoV-2 variant. Its sudden appearance points towards an animal reservoir, possibly mink. The protective role of past exposure and current vaccines against this variant should be evaluated.


Assuntos
COVID-19/genética , Genoma Viral , Mutação , SARS-CoV-2/genética , Sequenciamento Completo do Genoma , Animais , COVID-19/virologia , Epidemias , França/epidemiologia , Humanos , Vison/virologia , Epidemiologia Molecular , Filogenia , Reinfecção/virologia
18.
Gene ; 784: 145596, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33766711

RESUMO

The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) is rapidly spreading worldwide owing to its substantial transmission advantage. The variant has changes in critical sites of the spike protein with potential biological significance. Moreover, VOC-202012/01 has a mutation that inactivates the ORF8 protein, whose absence can change the clinical features of the infection. Why VOC-202012/01 is more transmissible remains unclear, but spike mutations and ORF8 inactivation stand out by their known phenotypic effects. Here I show that variants combining relevant spike mutations and the absence of ORF8 occurred in SARS-CoV-2 and related viruses circulating in other host species. A truncated ORF8 (Q23stop) occurred in a SARS-CoV-2-related virus from a pangolin seized in China in 2017, also with several mutations in critical spike sites. Strikingly, I found that variants without ORF8 (E19stop) and with the N501T spike mutation circulated in farmed mink and humans from Denmark. Although with differences to VOC-202012/01, the identification of these variants highlights the danger of having reservoirs of SARS-CoV-2 and related viruses where more transmissible variants may occur and spill over to humans.


Assuntos
COVID-19/veterinária , Vison/virologia , Pangolins/virologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais/genética , Animais , COVID-19/transmissão , COVID-19/virologia , China , Códon sem Sentido , Dinamarca , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Especificidade de Hospedeiro , Humanos , SARS-CoV-2/isolamento & purificação , Proteínas Virais/metabolismo
20.
Emerg Microbes Infect ; 10(1): 472-480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33657971

RESUMO

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive "mixing vessels" for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented.


Assuntos
Vírus da Influenza A/patogenicidade , Vison/virologia , Infecções por Orthomyxoviridae/transmissão , Animais , Modelos Animais de Doenças , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vírus da Influenza A Subtipo H9N2/imunologia , Vírus da Influenza A Subtipo H9N2/patogenicidade , Vírus da Influenza A/imunologia , Vison/imunologia , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Vírus Reordenados/imunologia , Vírus Reordenados/patogenicidade
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