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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
6.
Viruses ; 13(8)2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34452503

RESUMO

Recent outbreaks of zoonotic coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have caused tremendous casualties and great economic shock. Although some repurposed drugs have shown potential therapeutic efficacy in clinical trials, specific therapeutic agents targeting coronaviruses have not yet been developed. During coronavirus replication, a replicase gene cluster, including RNA-dependent RNA polymerase (RdRp), is alternatively translated via a process called -1 programmed ribosomal frameshift (-1 PRF) by an RNA pseudoknot structure encoded in viral RNAs. The coronavirus frameshifting has been identified previously as a target for antiviral therapy. In this study, the frameshifting efficiencies of MERS-CoV, SARS-CoV and SARS-CoV-2 were determined using an in vitro -1 PRF assay system. Our group has searched approximately 9689 small molecules to identify potential -1 PRF inhibitors. Herein, we found that a novel compound, 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline (KCB261770), inhibits the frameshifting of MERS-CoV and effectively suppresses viral propagation in MERS-CoV-infected cells. The inhibitory effects of 87 derivatives of furo[2,3-b]quinolines were also examined showing less prominent inhibitory effect when compared to compound KCB261770. We demonstrated that KCB261770 inhibits the frameshifting without suppressing cap-dependent translation. Furthermore, this compound was able to inhibit the frameshifting, to some extent, of SARS-CoV and SARS-CoV-2. Therefore, the novel compound 2-(5-acetylthiophen-2yl)furo[2,3-b]quinoline may serve as a promising drug candidate to interfere with pan-coronavirus frameshifting.


Assuntos
Antivirais/farmacologia , Mudança da Fase de Leitura do Gene Ribossômico/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Quinolinas/farmacologia , Vírus da SARS/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Células A549 , Animais , Linhagem Celular , Mudança da Fase de Leitura do Gene Ribossômico/fisiologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Vírus da SARS/genética , Vírus da SARS/fisiologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Bibliotecas de Moléculas Pequenas , Zoonoses Virais/virologia , Replicação Viral/efeitos dos fármacos
7.
Viruses ; 13(7)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34372585

RESUMO

Natural SARS-CoV-2 infection in pets has been widely documented during the last year. Although the majority of reports suggested that dogs' susceptibility to the infection is low, little is known about viral pathogenicity and transmissibility in the case of variants of concern, such as B.1.1.7 in this species. Here, as part of a large-scale study on SARS-CoV-2 prevalence in pets in Spain, we have detected the B.1.1.7 variant of concern (VOC) in a dog whose owners were infected with SARS-CoV-2. The animal did not present any symptoms, but viral loads were high in the nasal and rectal swabs. In addition, viral isolation was possible from both swabs, demonstrating that the dog was shedding infectious virus. Seroconversion occurred 23 days after the first sampling. This study documents the first detection of B.1.1.7 VOC in a dog in Spain and emphasizes the importance of performing active surveillance and genomic investigation on infected animals.


Assuntos
COVID-19/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/virologia , SARS-CoV-2/isolamento & purificação , Animais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Cães , Genoma Viral , Masculino , Mutação , SARS-CoV-2/genética , Análise de Sequência de DNA , Espanha/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Zoonoses Virais/diagnóstico , Zoonoses Virais/virologia
8.
Nature ; 597(7874): 103-108, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280951

RESUMO

The recent emergence of SARS-CoV-2 variants of concern1-10 and the recurrent spillovers of coronaviruses11,12 into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Anticorpos Amplamente Neutralizantes/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2/classificação , SARS-CoV-2/imunologia , Animais , Anticorpos Monoclonais/química , Anticorpos Antivirais/química , Anticorpos Antivirais/uso terapêutico , Anticorpos Amplamente Neutralizantes/química , COVID-19/imunologia , COVID-19/virologia , Reações Cruzadas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Evasão da Resposta Imune/genética , Evasão da Resposta Imune/imunologia , Mesocricetus/imunologia , Mesocricetus/virologia , Mutação , Testes de Neutralização , SARS-CoV-2/química , SARS-CoV-2/genética , Zoonoses Virais/imunologia , Zoonoses Virais/prevenção & controle , Zoonoses Virais/virologia
10.
Zoonoses Public Health ; 68(5): 474-482, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33934531

RESUMO

In humans, hepatitis E virus (HEV) is responsible for an acute enterically transmitted hepatitis, which can become chronic in immune-compromised patients. Genotypes 3 and 4 (HEV-3 and HEV-4) are zoonotic, and domestic pigs and wild boar are the main reservoirs. The occurrence of autochthonous cases in Europe, which have been increasing over the last 10 years, has been associated with food-borne zoonotic transmission of HEV-3, mainly linked to consumption of undercooked or raw pork products (sausages containing liver) and wild boar meat. Zoonotic HEV-3 strains are widespread on pig farms, but little information is available on the dynamic of HEV-3 infection within farms, among pigs. The aims of this study were to evaluate the prevalence of the infection among pigs of different ages along the production chain by the zoonotic HEVs, and to evaluate how long the virus may persist in the farm environment. The presence of HEV-RNA was investigated by real-time reverse transcription PCR (RT-PCR) in 281 test faecal pools over 19 months (2017-2019) on a two-site farrow-to-finish farm (about 1,000 sows), in Northern Italy. A total of 67/281 test faecal pools (23.8%) resulted positive for the presence of HEV-RNA (site 1: 59/221, 26.7%; site 2: 8/60, 13.3%). Nucleotide sequencing revealed a unique HEV-3 viral variant circulating during 19 months of surveillance. The same HEV-3 strain was detected in the same farm on 2012, indicating the persistence of the same virus over 7 years, and highlighting the role of the environment as a continuous source of infection on pig farms. The results confirmed the circulation of the zoonotic genotype HEV-3 in pigs before slaughtering.


Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/veterinária , Doenças dos Suínos/virologia , Animais , Fazendas , Fezes/virologia , Hepatite E/epidemiologia , Hepatite E/virologia , Vírus da Hepatite E/genética , Itália/epidemiologia , Filogenia , Vigilância da População , Suínos , Doenças dos Suínos/epidemiologia , Fatores de Tempo , Zoonoses Virais/epidemiologia , Zoonoses Virais/virologia
11.
Bioessays ; 43(7): e2100015, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34046923

RESUMO

RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2's origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.


Assuntos
COVID-19/virologia , Quirópteros/virologia , Pangolins/virologia , Vírus da SARS/genética , SARS-CoV-2/classificação , SARS-CoV-2/genética , Incerteza , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/epidemiologia , COVID-19/transmissão , Conjuntos de Dados como Assunto , Furina/metabolismo , Humanos , Pandemias , Filogenia , Vírus da SARS/classificação , Vírus da SARS/isolamento & purificação , SARS-CoV-2/isolamento & purificação , Deleção de Sequência/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
13.
Parasit Vectors ; 14(1): 194, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832527

RESUMO

BACKGROUND: Infectious blood meal experiments have been frequently performed with different virus-vector combinations to assess the transmission potential of arthropod-borne (arbo)viruses. A wide variety of host blood sources have been used to deliver arboviruses to their arthropod vectors in laboratory studies. The type of blood used during vector competence experiments does not always reflect the blood from the viremic vertebrate hosts in the field, but little is known about the effect of blood source on the experimental outcome of vector competence studies. Here we investigated the effect of avian versus human blood on the infection and transmission rates of the zoonotic Usutu virus (USUV) in its primary mosquito vector Culex pipiens. METHODS: Cx. pipiens biotypes (pipiens and molestus) were orally infected with USUV through infectious blood meals containing either chicken or human whole blood. The USUV infection and transmission rates were determined by checking mosquito bodies and saliva for USUV presence after 14 days of incubation at 28 °C. In addition, viral titers were determined for USUV-positive mosquito bodies and saliva. RESULTS: Human and chicken blood lead to similar USUV transmission rates for Cx. pipiens biotype pipiens (18% and 15%, respectively), while human blood moderately but not significantly increased the transmission rate (30%) compared to chicken blood (17%) for biotype molestus. USUV infection rates with human blood were consistently higher in both Cx. pipiens biotypes compared to chicken blood. In virus-positive mosquitoes, USUV body and saliva titers did not differ between mosquitoes taking either human or chicken blood. Importantly, biotype molestus had much lower USUV saliva titers compared to biotype pipiens, regardless of which blood was offered. CONCLUSIONS: Infection of mosquitoes with human blood led to higher USUV infection rates as compared to chicken blood. However, the blood source had no effect on the vector competence for USUV. Interestingly, biotype molestus is less likely to transmit USUV compared to biotype pipiens due to very low virus titers in the saliva.


Assuntos
Culex/fisiologia , Infecções por Flavivirus/veterinária , Infecções por Flavivirus/virologia , Flavivirus/fisiologia , Mosquitos Vetores/fisiologia , Doenças das Aves Domésticas/virologia , Animais , Sangue/virologia , Galinhas/virologia , Culex/virologia , Comportamento Alimentar , Flavivirus/genética , Flavivirus/isolamento & purificação , Infecções por Flavivirus/sangue , Infecções por Flavivirus/transmissão , Humanos , Mosquitos Vetores/virologia , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/transmissão , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
14.
J Gen Virol ; 102(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33847554

RESUMO

Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.


Assuntos
Gastroenterite/virologia , Genoma Viral , Infecções por Rotavirus/virologia , Rotavirus , Zoonoses Virais/virologia , Adolescente , Animais , Bovinos/virologia , Feminino , Genótipo , Humanos , Japão , Rotavirus/genética , Rotavirus/isolamento & purificação
17.
Nat Commun ; 12(1): 1653, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712573

RESUMO

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, an experimental set-up is used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses cause a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmits efficiently. Serological assays confirm all virus transmission events. Although the experiments do not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while traveling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for virus transmission via the air between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.


Assuntos
Microbiologia do Ar , COVID-19/transmissão , Furões/virologia , Vírus da SARS , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/transmissão , Aerossóis , Substituição de Aminoácidos , Pelo Animal/virologia , Animais , COVID-19/virologia , Modelos Animais de Doenças , Feminino , Fômites/virologia , Vírus da Influenza A Subtipo H1N1 , Modelos Biológicos , Infecções por Orthomyxoviridae/transmissão , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/genética , Síndrome Respiratória Aguda Grave/virologia , Fatores de Tempo , Carga Viral , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Eliminação de Partículas Virais
19.
PLoS Biol ; 19(3): e3001115, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33711012

RESUMO

Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant adaptation to humans since the start of the Coronavirus Disease 2019 (COVID-19) pandemic and to October 2020. Here we assess the types of natural selection taking place in Sarbecoviruses in horseshoe bats versus the early SARS-CoV-2 evolution in humans. While there is moderate evidence of diversifying positive selection in SARS-CoV-2 in humans, it is limited to the early phase of the pandemic, and purifying selection is much weaker in SARS-CoV-2 than in related bat Sarbecoviruses. In contrast, our analysis detects evidence for significant positive episodic diversifying selection acting at the base of the bat virus lineage SARS-CoV-2 emerged from, accompanied by an adaptive depletion in CpG composition presumed to be linked to the action of antiviral mechanisms in these ancestral bat hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor about 1976), is a recombinant with a structure that includes differential CpG content in Spike; clear evidence of coinfection and evolution in bats without involvement of other species. While an undiscovered "facilitating" intermediate species cannot be discounted, collectively, our results support the progenitor of SARS-CoV-2 being capable of efficient human-human transmission as a consequence of its adaptive evolutionary history in bats, not humans, which created a relatively generalist virus.


Assuntos
COVID-19/virologia , Quirópteros/virologia , SARS-CoV-2/genética , Zoonoses Virais/virologia , Animais , COVID-19/epidemiologia , COVID-19/transmissão , Evolução Molecular , Genoma Viral , Especificidade de Hospedeiro , Humanos , Pandemias , Filogenia , Receptores Virais/genética , SARS-CoV-2/patogenicidade , Seleção Genética , Zoonoses Virais/genética , Zoonoses Virais/transmissão
20.
Virus Res ; 297: 198382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33705799

RESUMO

Coronaviruses are a large group of RNA viruses that infect a wide range of animal species. The replication strategy of coronaviruses involves recombination and mutation events that lead to the possibility of cross-species transmission. The high plasticity of the viral receptor due to a continuous modification of the host species habitat may be the cause of cross-species transmission that can turn into a threat to other species including the human population. The successive emergence of highly pathogenic coronaviruses such as the Severe Acute Respiratory Syndrome (SARS) in 2003, the Middle East Respiratory Syndrome Coronavirus in 2012, and the recent SARS-CoV-2 has incentivized a number of studies on the molecular basis of the coronavirus and its pathogenesis. The high degree of interrelatedness between humans and wild and domestic animals and the modification of animal habitats by human urbanization, has favored new viral spreads. Hence, knowledge on the main clinical signs of coronavirus infection in the different hosts and the distinctive molecular characteristics of each coronavirus is essential to prevent the emergence of new coronavirus diseases. The coronavirus infections routinely studied in veterinary medicine must be properly recognized and diagnosed not only to prevent animal disease but also to promote public health.


Assuntos
Infecções por Coronavirus , Coronavirus , Especificidade de Hospedeiro , Zoonoses Virais , Animais , Coronavirus/química , Coronavirus/genética , Coronavirus/fisiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Genoma Viral , Humanos , Fases de Leitura Aberta , RNA Viral , Proteínas Virais , Estruturas Virais , Transcrição Viral , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Montagem de Vírus , Replicação Viral
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