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1.
Genome Biol ; 24(1): 13, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683094

RESUMO

BACKGROUND: The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. RESULTS: Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. CONCLUSION: Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril.


Assuntos
Anseriformes , Influenza Aviária , Animais , Transcriptoma , Células Endoteliais , Austrália
2.
PLoS Biol ; 20(8): e3001728, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35913989

RESUMO

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Criança , Células Epiteliais , Humanos , SARS-CoV-2/genética
3.
Front Cell Infect Microbiol ; 11: 714440, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595130

RESUMO

People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Diabetes Mellitus Tipo 1/complicações , Humanos , Influenza Humana/complicações , Camundongos , Infecções por Orthomyxoviridae/complicações
4.
Elife ; 102021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33588989

RESUMO

Influenza virus has a high mutation rate, such that within one host different viral variants can emerge. Evidence suggests that influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. We have recently shown that the non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production. Here, we seek to address if this is associated with an increased emergence of influenza virus variants. Compared to controls, mice with paucigranulocytic asthma had increased disease severity and an increased emergence of influenza virus variants. Specifically, PB1 mutations exclusively detected in asthmatic mice were associated with increased polymerase activity. Furthermore, asthmatic host-derived virus led to increased disease severity in wild-type mice. Taken together, these data suggest that at least a subset of patients with asthma may be more susceptible to severe influenza and may be a possible source of new influenza virus variants.


Assuntos
Asma/virologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/virologia , Animais , Feminino , Interações Hospedeiro-Patógeno , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor para Produtos Finais de Glicação Avançada/deficiência
5.
Clin Infect Dis ; 72(12): e1146-e1153, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33283240

RESUMO

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Criança , Características da Família , Humanos , Incidência , Pandemias
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