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1.
Nature ; 583(7815): 286-289, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380510

RESUMO

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.


Assuntos
Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Eutérios/virologia , Evolução Molecular , Genoma Viral/genética , Homologia de Sequência do Ácido Nucleico , Animais , Betacoronavirus/classificação , COVID-19 , China , Quirópteros/virologia , Chlorocebus aethiops , Proteínas do Envelope de Coronavírus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Proteínas M de Coronavírus , Proteínas do Nucleocapsídeo de Coronavírus , Reservatórios de Doenças/virologia , Genômica , Especificidade de Hospedeiro , Humanos , Pulmão/patologia , Pulmão/virologia , Malásia , Proteínas do Nucleocapsídeo/genética , Pandemias , Fosfoproteínas , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , Recombinação Genética , SARS-CoV-2 , Alinhamento de Sequência , Análise de Sequência de RNA , Glicoproteína da Espícula de Coronavírus/genética , Células Vero , Proteínas do Envelope Viral/genética , Proteínas da Matriz Viral/genética , Zoonoses/transmissão , Zoonoses/virologia
2.
PLoS Pathog ; 19(5): e1011384, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37196026

RESUMO

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.


Assuntos
COVID-19 , Quirópteros , Animais , Humanos , Pangolins/genética , SARS-CoV-2/genética , Virulência , Filogenia , RNA Viral , Tropismo
3.
Parasitol Res ; 123(10): 349, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392533

RESUMO

Blood parasites from the order Haemosporida infect many vertebrates and cause malaria-like diseases. In this study, a haemosporidian infection was detected in a sick grey crowned crane imported into China using a combination of morphological and molecular approaches. Blood samples were collected from the jugular vein and processed for morphological identification of infective parasites using stained blood smears and microscopy. No merogony occurs in the blood cells, and sporadic pigment granules were observed. Nested-PCR assays were employed for a molecular examination, which indicated that the cytb gene of this parasite had 94.1-94.9% identity to Haemoproteus antigonis. Subsequently, its mitochondrial genome structure was determined by high-throughput sequencing using the DNBSEQ-T7 platform. The determined structure was confirmed by the Sanger sequencing using amplicons. The mitochondrial genome obtained for this parasite exhibited a low CG content (32.0%) and possessed three protein-coding genes, encoding 1068 amino acids, which constituted 53.7% of the genome. Phylogenetic analysis indicated that this parasite clustered with Haemoproteus sp. is detected in grey crowned cranes from Africa. This parasite was likely acquired during importation of this animal; thus, strict quarantine of imported ornamental animals is required to prevent the entry of new pathogens.


Assuntos
Doenças das Aves , Aves , Haemosporida , Filogenia , Infecções Protozoárias em Animais , Animais , China , Haemosporida/genética , Haemosporida/isolamento & purificação , Haemosporida/classificação , Infecções Protozoárias em Animais/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Doenças das Aves/parasitologia , Doenças das Aves/epidemiologia , Aves/parasitologia , Genoma Mitocondrial/genética , Reação em Cadeia da Polimerase , Sequenciamento de Nucleotídeos em Larga Escala , Citocromos b/genética
4.
Virus Genes ; 59(6): 845-851, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37851282

RESUMO

The virus that causes Marek's disease (MD) is globally ubiquitous in chickens, continuously evolving, and poses a significant threat to the poultry industry. Although vaccines are extensively used, MD still occurs frequently and the virus has evolved increased virulence in China. Here, we report an outbreak of MD in vaccinated chickens and unvaccinated turkeys in a backyard farm in Guangdong province, China, in 2018. Phylogenetic analysis revealed two lineages of MDVs at this farm, with one lineage, containing isolates from two turkeys and five chickens, clustering with virulent Chinese strains and displays a relatively high genetic divergence from the vaccine strains. These new isolates appear to have broken through vaccine immunity, yielding this outbreak of MD in chickens and turkeys. The second lineage included four chicken isolates that clustered with the CVI988 and 814 vaccine strains. The large diversity of MDVs in this single outbreak reveals a complex circulation of MDVs in China. Poor breeding conditions and the weak application of disease prevention and control measures make backyard farms a hotbed for the evolution of viruses that cause infectious diseases. This is especially important in MDV as the MD vaccines do not provide sterilizing immunity, which allows the replication and shedding of virulent field viruses by vaccinated individuals and supporting the continuous evolution of MDVs. Hence, constant monitoring of the evolution of MDVs is necessary to understand the evolution of these field viruses and potential expansions of their host range.


Assuntos
Herpesvirus Galináceo 2 , Doença de Marek , Doenças das Aves Domésticas , Vacinas , Humanos , Animais , Galinhas , Filogenia , Perus , Herpesvirus Galináceo 2/genética , Evolução Molecular
6.
J Gen Virol ; 102(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33843572

RESUMO

The identification of SARS-CoV-2-like viruses in Malayan pangolins (Manis javanica) has focused attention on these endangered animals and the viruses they carry. We successfully isolated a novel respirovirus from the lungs of a dead Malayan pangolin. Similar to murine respirovirus, the full-length genome of this novel virus was 15 384 nucleotides comprising six genes in the order 3'-(leader)-NP-P-M-F-HN-l-(trailer)-5'. Phylogenetic analysis revealed that this virus belongs to the genus Respirovirus and is most closely related to murine respirovirus. Notably, animal infection experiments indicated that the pangolin virus is highly pathogenic and transmissible in mice, with inoculated mice having variable clinical symptoms and a fatality rate of 70.37 %. The virus was found to replicate in most tissues with the exception of muscle and heart. Contact transmission of the virus was 100 % efficient, although the mice in the contact group displayed milder symptoms, with the virus mainly being detected in the trachea and lungs. The isolation of a novel respirovirus from the Malayan pangolin provides new insight into the evolution and distribution of this important group of viruses and again demonstrates the potential infectious disease threats faced by endangered pangolins.


Assuntos
Pangolins/virologia , Infecções por Respirovirus , Respirovirus , Animais , Espécies em Perigo de Extinção , Feminino , Genoma Viral , Camundongos , Filogenia , Respirovirus/classificação , Respirovirus/isolamento & purificação , Respirovirus/patogenicidade , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/veterinária , Infecções por Respirovirus/virologia
7.
Nature ; 522(7554): 102-5, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25762140

RESUMO

Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3-7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.


Assuntos
Galinhas/virologia , Evolução Molecular , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Animais , China/epidemiologia , Ecossistema , Genótipo , Humanos , Subtipo H7N9 do Vírus da Influenza A/classificação , Influenza Aviária/transmissão , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Influenza Humana/virologia , Dados de Sequência Molecular , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Zoonoses/transmissão , Zoonoses/virologia
8.
J Cell Mol Med ; 23(5): 3178-3189, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30821089

RESUMO

Radiation-induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of post-irradiation dermatitis, which remains a significant clinical problem. Resolving this challenge requires gaining a better understanding of the precise pathophysiology, which in turn requires establishment of a suitable animal model that mimics the clinical condition, and can also be used to investigate the mechanism and explore effective treatment options. In this study, a single dose of 90 Gy irradiation to rats resulted in ulceration, dermal thickening, inflammation, hair follicle loss, and sebaceous glands loss, indicating successful establishment of the model. Few hair follicle cells migrated to form epidermal cells, and both the severity of skin fibrosis and hydroxyproline levels increased with time post-irradiation. Radiation damaged the mitochondria and induced both apoptosis and autophagy of the skin cells. Therefore, irradiation of 90 Gy can be used to successfully establish a rat model of radiation-induced dermatitis. This model will be helpful for developing new treatments and gaining a better understanding of the pathological mechanism of radiation-induced dermatitis. Specifically, our results suggest autophagy regulation as a potentially effective therapeutic target.


Assuntos
Modelos Animais de Doenças , Neoplasias/radioterapia , Lesões Experimentais por Radiação/patologia , Radiodermite/patologia , Animais , Apoptose/efeitos da radiação , Movimento Celular/efeitos da radiação , Folículo Piloso/patologia , Folículo Piloso/efeitos da radiação , Humanos , Neoplasias/complicações , Doses de Radiação , Radioterapia/efeitos adversos , Ratos , Pele/patologia , Pele/efeitos da radiação
9.
Biochem Biophys Res Commun ; 516(1): 120-126, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196622

RESUMO

Limited is known about role of gut microbiota in the metabolism of high-altitude-living herbivores, and potential co-evolution between gut microbiome and host genome during high altitude adaptation were not fully understood. Here, DNA from faecal samples was used to investigate the gut microbial compositions and diversity in three host species endemic to the high-altitude Tibetan plateau, the Tibetan antelope (Pantholops hodgsonii, T-antelope, 4300 m) and the Tibetan wild ass (Equus kiang, T-ass, 4300 m), and in the Tibetan sheep (Ovis aries, T-sheep) collected from two different altitudes (T-sheep [k], 4300 m and T-sheep [l] 3000 m). Ordinary sheep (O. aries, sheep) from low altitudes (1800 m) were used for comparison. 16S rRNA gene sequencing revealed that the genera Ruminococcus (22.78%), Oscillospira (20.00%), and Clostridium (10.00%) were common taxa in all high-altitude species (T-antelope, T-ass and T-sheep [k]). Ruminococcaceae, Clostridiales, Clostridia, and Firmicutes showed greater enrichment in the T-antelopes' gut microbiota than in the microbiota of lower-altitude sheep (T-sheep [l] and sheep). The T-antelopes' gut microbiota displayed a higher ratio of Firmicutes to Bacteroidetes than lower-altitude sheep (T-sheep [l] and sheep). A functional capacity analysis of the paired-end metagenomics sequences of the gut metagenomes of high-altitude T-antelopes and T-sheep annotated over 80% of the unique genes to metabolism (especially carbohydrate metabolism pathways) and genetic information processing in the Kyoto Encyclopedia of Genes and Genomes database. The gut metagenome of the T-antelope may have co-evolved with the host genomes (e.g. glycolysis and DNA repair). The higher-altitude herbivores tended to have similar gut microbial compositions, with similar functional capacities, suggesting that their gut microbiota could involved in their high-altitude adaptation.


Assuntos
Antílopes/microbiologia , Equidae/microbiologia , Microbioma Gastrointestinal , Ovinos/microbiologia , Aclimatação , Altitude , Animais , Antílopes/fisiologia , Equidae/fisiologia , Fezes/microbiologia , Metagenoma , Ovinos/fisiologia , Tibet
10.
Nature ; 502(7470): 241-4, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-23965623

RESUMO

A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.


Assuntos
Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Humana/virologia , Filogenia , Animais , Galinhas , China , Patos , Genes Virais/genética , Humanos , Vírus da Influenza A Subtipo H7N7/classificação , Vírus da Influenza A Subtipo H7N7/genética , Vírus da Influenza A Subtipo H9N2/classificação , Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/transmissão , Dados de Sequência Molecular , Vírus Reordenados/classificação , Vírus Reordenados/genética
11.
J Infect Dis ; 217(11): 1699-1707, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29438519

RESUMO

Background: Avian influenza A virus H7N9 has caused 5 epidemic waves of human infections in China since 2013. Avian influenza A viruses may face strong selection to adapt to novel conditions when establishing themselves in humans. In this study, we sought to determine whether adaptive evolution had occurred in human-isolated H7N9 viruses. Methods: We evaluated all available genomes of H7N9 avian influenza A virus. Maximum likelihood trees were separately reconstructed for all 8 genes. Signals of positive selection and convergent evolution were then detected on branches that lead to changes in host tropism (from avian to human). Results: We found that 3 genes had significant signals of positive selection (all of them P < .05). In addition, we detected 34 sites having significant signals for parallel evolution in 8 genes (all of them P < .05), including 7 well-known sites (Q591K, E627K, and D701N in PB2 gene; R156K, V202A, and L244Q in HA; and R289K in NA) that play roles in crossing species barriers for avian influenza A viruses. Conclusion: Our study suggests that, during infection in humans, H7N9 viruses have undergone adaptive evolution to adapt to their new host environment and that the sites where parallel evolution occurred might play roles in crossing species barriers and respond to the new selection pressures arising from their new host environments.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/virologia , Proteínas Virais/genética , Evolução Biológica , China , Humanos , Tropismo Viral/genética
12.
PLoS Genet ; 8(6): e1002788, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22761589

RESUMO

The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators--two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function.


Assuntos
Caderinas/genética , Quirópteros , Golfinhos , Ecolocação/fisiologia , Proteínas de Membrana/genética , Animais , Córtex Auditivo/metabolismo , Percepção Auditiva/genética , Percepção Auditiva/fisiologia , Caderinas/fisiologia , Quirópteros/genética , Quirópteros/fisiologia , Nervo Coclear/fisiologia , Golfinhos/genética , Golfinhos/psicologia , Evolução Molecular , Expressão Gênica , Proteínas de Membrana/fisiologia , Dados de Sequência Molecular , Mutação , Filogenia , Seleção Genética
13.
iScience ; 27(2): 108962, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38322989

RESUMO

Newcastle disease is a global problem that causes huge economic losses and threatens the health and welfare of poultry. Despite the knowledge gained on the metabolic impact of NDV on cells, the extent to which infection modifies the plasma metabolic network in chickens remains unknown. Herein, we performed targeted metabolomic and lipidomic to create a plasma metabolic network map during NDV infection. Meanwhile, we used single-cell RNA sequencing to explore the heterogeneity of lung tissue cells in response to NDV infection in vivo. The results showed that NDV remodeled the plasma phospholipid metabolism network. NDV preferentially targets infected blood endothelial cells, antigen-presenting cells, fibroblasts, and neutrophils in lung tissue. Importantly, NDV may directly regulate ribosome protein transcription to facilitate efficient viral protein translation. In conclusion, NDV infection remodels the plasma phospholipid metabolism network in chickens. This work provides valuable insights to further understand the pathogenesis of NDV.

14.
One Health ; 18: 100750, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38798737

RESUMO

Cryptosporidium spp., Giardia spp. and Enterocytozoon bieneusi are common zoonotic pathogens in humans and animals. Although rodents are important parts of the ecosystem and common hosts for these pathogens, little is known of the distribution, genetic diversity and zoonotic potential of these pathogens in wild rodents. A total of 442 fecal samples were collected from eleven wild rodent species in three provinces of China, and analyzed for these pathogens by PCR and DNA sequencing. The infection rates of Cryptosporidium spp., Giardia spp. and E. bieneusi were 19.9% (88/442), 19.8% (75/378) and 12.2% (54/442), respectively. Altogether, 23 known Cryptosporidium species/genotypes were identified and their distribution varied among different sampling locations or rodent species. Subtyping of the zoonotic Cryptosporidium species identified two novel subtype families XVe and XVf in C. viatorum, the subtype family XIIh and a novel subtype family XIIj in C. ubiquitum, and the subtype family IId in C. parvum. Three Giardia species were identified, including G. microti (n = 57), G. muris (n = 15) and G. duodenalis (n = 3), with G. duodenalis assemblages A and G identified in brown rats in urban areas of Guangdong. In addition, 13 E. bieneusi genotypes including eight known and five novel ones were identified, belonging to Groups 1, 2, 10, 14 and 15. Within nine genotypes in the zoonotic Group 1, common human-pathogenic genotypes D, Type IV, PigEbITS7 and Peru8 were detected only in brown rats and Lesser rice-field rats in urban areas of Guangdong. Apparent host adaptation and geographical differences were observed among Cryptosporidium spp., Giardia spp. and E. bieneusi genotypes in wild rodents in the present study. Furthermore, the zoonotic Cryptosporidium species and E. bieneusi genotypes commonly found here suggest a high zoonotic potential of these pathogens in wild rodents, especially in brown rats in urban areas. Hygiene and One Health measures should be implemented in urban streets and food stores to reduce the possible direct and indirect transmission of these rodent-related pathogens.

15.
mSphere ; : e0055124, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39345123

RESUMO

The discovery of severe acute respiratory syndrome-coronavirus-2-like and Middle East respiratory syndrome-coronavirus-like viruses in Malayan pangolins has raised concerns about their potential role in the spread of zoonotic diseases. Herein, we describe the isolation and whole-genome sequencing of potentially zoonotic two bacterial pathogens from diseased Malaysian pangolins (Manis javanica)-Corynebacterium ulcerans and Erysipelothrix sp. The newly identified species were designated as C. ulcerans P69 and Erysipelothrix sp. P66. C. ulcerans P69 exhibited 99.2% whole-genome nucleotide identity to human bacterial isolate 4940, suggesting that it might have zoonotic potential. Notably, C. ulcerans P69 lacked the diphtheria toxin (tox) gene that is widely used in vaccines to protect humans from corynebacterial infection, which suggests that the current vaccine may be of limited efficacy against this pangolin strain. C. ulcerans P69 also contains other known virulence-associated genes such as pld and exhibits resistance to several antibiotics (erythromycin, clindamycin, penicillin G, gentamicin, tetracycline), which may affect its effective control. Erysipelothrix sp. P66 was closely related to Erysipelothrix sp. strain 2-related strains, exhibiting 98.8% whole-genome nucleotide identity. This bacterium is lethal in mice, and two commercial vaccines failed to protect its challenge, such that it could potentially pose a threat to the swine industry. Overall, this study highlights that, in addition to viruses, pangolins harbor bacteria that may pose a potential threat to humans and domestic animals, and which merit attention. IMPORTANCE: This study firstly reports the presence of two potentially zoonotic bacteria, Corynebacterium ulcerans and Erysipelothrix sp., in diseased Malaysian pangolins collected in 2019. The pangolin C. ulcerans is lethal in mice and resists many antibiotics. It clustered with a lethal human strain but lacked the diphtheria toxin gene. Diphtheria toxin is widely used as a vaccine around the world to protect humans from the infection of corynebacteria. The lack of the tox gene suggests that the current vaccine may be of limited efficacy against this pangolin strain. The pangolin Erysipelothrix sp. is the sister clade of Erysipelothrix rhusiopathiae. It is lethal in mice, and two commercial vaccines failed to protect the mice against challenge with the pangolin Erysipelothrix sp., such that this strain could potentially pose a threat to the swine industry. These findings emphasize the potential threat of pangolin bacteria.

16.
Proc Natl Acad Sci U S A ; 107(19): 8666-71, 2010 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-20421465

RESUMO

Bat flight poses intriguing questions about how flight independently developed in mammals. Flight is among the most energy-consuming activities. Thus, we deduced that changes in energy metabolism must be a primary factor in the origin of flight in bats. The respiratory chain of the mitochondrial produces 95% of the adenosine triphosphate (ATP) needed for locomotion. Because the respiratory chain has a dual genetic foundation, with genes encoded by both the mitochondrial and nuclear genomes, we examined both genomes to gain insights into the evolution of flight within mammals. Evidence for positive selection was detected in 23.08% of the mitochondrial-encoded and 4.90% of nuclear-encoded oxidative phosphorylation (OXPHOS) genes, but in only 2.25% of the nuclear-encoded nonrespiratory genes that function in mitochondria or 1.005% of other nuclear genes in bats. To address the caveat that the two available bat genomes are of only draft quality, we resequenced 77 OXPHOS genes from four species of bats. The analysis of the resequenced gene data are in agreement with our conclusion that a significantly higher proportion of genes involved in energy metabolism, compared with background genes, show evidence of adaptive evolution specific on the common ancestral bat lineage. Both mitochondrial and nuclear-encoded OXPHOS genes display evidence of adaptive evolution along the common ancestral branch of bats, supporting our hypothesis that genes involved in energy metabolism were targets of natural selection and allowed adaptation to the huge change in energy demand that were required during the origin of flight.


Assuntos
Adaptação Fisiológica/genética , Quirópteros/genética , Quirópteros/fisiologia , Metabolismo Energético/genética , Evolução Molecular , Voo Animal/fisiologia , Animais , Humanos , Dados de Sequência Molecular , Filogenia , Roedores/genética , Seleção Genética
17.
Microbiome ; 11(1): 163, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496083

RESUMO

BACKGROUND: Antibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment. RESULTS: Unexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection. CONCLUSIONS: Our data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Vírus da Influenza A Subtipo H9N2 , Microbiota , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Microbioma Gastrointestinal/genética , Vírus da Influenza A Subtipo H9N2/genética , Galinhas/microbiologia
18.
Cell Discov ; 9(1): 59, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330497

RESUMO

Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.

19.
Nat Commun ; 14(1): 2488, 2023 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120646

RESUMO

Wildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.


Assuntos
COVID-19 , Quirópteros , Vírus , Animais , Animais Domésticos/virologia , Animais Selvagens/virologia , Animais de Zoológico/virologia , Quirópteros/virologia , Mamíferos/virologia , Pangolins/virologia , Filogenia , Zoonoses/virologia
20.
Mol Biol Evol ; 28(1): 39-44, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20924083

RESUMO

Mitochondria are the power plant of cells, which play critical roles not only in energy metabolism but also in thermoregulation. These two roles have been individually suggested to influence mitochondrial DNA (mtDNA) evolution, however their relative importance is still rarely considered. Here, we conduct a comparative genomic analysis of 401 teleost complete mitochondrial genomes and test the roles of these dual functional constraints on mitochondria to provide a more complete view of mtDNA evolution. We found that mitochondrial protein-coding genes of migratory fishes have significantly smaller Ka/Ks than nonmigratory fishes. The same data set showed that the genes of fishes living in cold climates have significantly smaller Ka/Ks than tropical fishes. In contrast, these trends were not observed for two nuclear genes that are not involved in energy metabolism. The differences in selection patterns observed between mitochondrial and nuclear genes suggest that the functional constraints acting on mitochondria, due to energy metabolism and/or thermoregulation, influence the evolution of mitochondrial-encoded proteins in teleosts.


Assuntos
Evolução Molecular , Peixes/genética , Peixes/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Animais , Regulação da Temperatura Corporal/genética , Metabolismo Energético/genética , Genoma Mitocondrial
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