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1.
Int J Med Microbiol ; 314: 151609, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286065

RESUMO

Interspecies transmission of influenza A viruses (IAV) from pigs to humans is a concerning event as porcine IAV represent a reservoir of potentially pandemic IAV. We conducted a comprehensive analysis of two porcine A(H1N1)v viruses isolated from human cases by evaluating their genetic, antigenic and virological characteristics. The HA genes of those human isolates belonged to clades 1C.2.1 and 1C.2.2, respectively, of the A(H1N1) Eurasian avian-like swine influenza lineage. Antigenic profiling revealed substantial cross-reactivity between the two zoonotic H1N1 viruses and human A(H1N1)pdm09 virus and some swine viruses, but did not reveal cross-reactivity to H1N2 and earlier human seasonal A(H1N1) viruses. The solid-phase direct receptor binding assay analysis of both A(H1N1)v showed a predominant binding to α2-6-sialylated glycans similar to human-adapted IAV. Investigation of the replicative potential revealed that both A(H1N1)v viruses grow in human bronchial epithelial cells to similar high titers as the human A(H1N1)pdm09 virus. Cytokine induction was studied in human alveolar epithelial cells A549 and showed that both swine viruses isolated from human cases induced higher amounts of type I and type III IFN, as well as IL6 compared to a seasonal A(H1N1) or a A(H1N1)pdm09 virus. In summary, we demonstrate a remarkable adaptation of both zoonotic viruses to propagate in human cells. Our data emphasize the needs for continuous monitoring of people and regions at increased risk of such trans-species transmissions, as well as systematic studies to quantify the frequency of these events and to identify viral molecular determinants enhancing the zoonotic potential of porcine IAV.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Orthomyxoviridae , Doenças dos Suínos , Humanos , Animais , Suínos , Vírus da Influenza A Subtipo H1N1/genética , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Influenza Humana/epidemiologia , Alemanha/epidemiologia , Doenças dos Suínos/epidemiologia , Filogenia
2.
Artigo em Alemão | MEDLINE | ID: mdl-34878564

RESUMO

Disinfection measures have become more important as a result of the COVID-19 pandemic in Germany. The increased need for disinfectants at the beginning of the pandemic required temporary legal regulations in order to provide a sufficient quantity of products for the necessary disinfection in the medical sector on the one hand and for the additional demand in the population on the other. For this purpose, the Federal Institute for Drugs and Medical Devices (BfArM) and the Federal Institute for Occupational Safety and Health (BAuA) issued a general ruling, which is explained in more detail in this article. The focus was on measures for hygienic hand disinfection. However, other applications such as surface disinfection in relation to pandemic respiratory diseases are also addressed. The experience gained in ensuring the supply of disinfectants that are effective and safe to use should be used to prepare for further pandemics.


Assuntos
COVID-19 , Desinfetantes , Desinfecção , Alemanha , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
3.
J Virol ; 89(14): 6982-93, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25903337

RESUMO

UNLABELLED: Influenza A virus (IAV) infection provokes an antiviral response involving the expression of type I and III interferons (IFN) and IFN-stimulated genes (ISGs) in infected cell cultures. However, the spatiotemporal dynamics of the IFN reaction are incompletely understood, as previous studies investigated mainly the population responses of virus-infected cultures, although substantial cell-to-cell variability has been documented. We devised a fluorescence-activated cell sorting-based assay to simultaneously quantify expression of viral antigens and ISGs, such as ISG15, MxA, and IFIT1, in IAV-infected cell cultures at the single-cell level. This approach revealed that seasonal IAV triggers an unexpected asymmetric response, as the major cell populations expressed either viral antigen or ISG, but rarely both. Further investigations identified a role of the viral NS1 protein in blocking ISG expression in infected cells, which surprisingly did not reduce paracrine IFN signaling to noninfected cells. Interestingly, viral ISG control was impaired in cultures infected with avian-origin IAV, including the H7N9 virus from eastern China. This phenotype was traced back to polymorphic NS1 amino acids known to be important for stable binding of the polyadenylation factor CPSF30 and concomitant suppression of host cell gene expression. Most significantly, mutation of two amino acids within the CPSF30 attachment site of NS1 from seasonal IAV diminished the strict control of ISG expression in infected cells and substantially attenuated virus replication. In conclusion, our approach revealed an asymmetric, NS1-dependent ISG induction in cultures infected with seasonal IAV, which appears to be essential for efficient virus propagation. IMPORTANCE: Interferons are expressed by infected cells in response to IAV infection and play important roles in the antiviral immune response by inducing hundreds of interferon-stimulated genes (ISGs). Unlike many previous studies, we investigated the ISG response at the single-cell level, enabling novel insights into this virus-host interaction. Hence, cell cultures infected with seasonal IAV displayed an asymmetric ISG induction that was confined almost exclusively to noninfected cells. In comparison, ISG expression was observed in larger cell populations infected with avian-origin IAV, suggesting a more resolute antiviral response to these strains. Strict control of ISG expression by seasonal IAV was explained by the binding of the viral NS1 protein to the polyadenylation factor CPSF30, which reduces host cell gene expression. Mutational disruption of CPSF30 binding within NS1 concomitantly attenuated ISG control and replication of seasonal IAV, illustrating the importance of maintaining an asymmetric ISG response for efficient virus propagation.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Vírus da Influenza A/imunologia , Interferons/metabolismo , China , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Citometria de Fluxo/métodos , Humanos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Análise de Célula Única , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
4.
J Infect Dis ; 206(11): 1685-94, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22829640

RESUMO

BACKGROUND: Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied. METHODS: We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures. RESULTS: Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses. CONCLUSIONS: These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.


Assuntos
Células Epiteliais Alveolares/classificação , Células Epiteliais Alveolares/virologia , Vírus da Influenza A/fisiologia , Tropismo Viral/fisiologia , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/patogenicidade , Influenza Humana/virologia , Pulmão/citologia , Macrófagos Alveolares/virologia , Técnicas de Cultura de Tecidos , Virulência , Replicação Viral/fisiologia
5.
Comp Med ; 56(3): 196-201, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16774128

RESUMO

Recent studies have shown that 'return to home cage' can serve as a reward for maze learning in adult male mice. The present study examined whether the same reward is an effective motivator of learning in young and old mice and included females in the study design. We tested 25- and 65-d-old HS mice and 85- and 800-d-old B6D2F2 mice in a Lashley III maze. Return to home cage motivated maze acquisition in all groups. Compared with 65-d-old HS mice, 25-d-olds acquired the maze more slowly, took longer to achieve the test criterion, and showed increased latency to reach the goal box. There was no difference between 85- and 800-d-old B6D2F2 mice in rate of acquisition. This reward procedure may reduce the potentially confounding effects of deprivation or aversive stimuli on maze performance and may be suitable as a motivational procedure for a wide range of subject groups.


Assuntos
Envelhecimento/genética , Comportamento de Retorno ao Território Vital/fisiologia , Aprendizagem em Labirinto/fisiologia , Modelos Animais , Recompensa , Meio Social , Animais , Feminino , Genótipo , Masculino , Rememoração Mental , Camundongos , Camundongos Endogâmicos , Motivação , Orientação
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