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3.
J Infect Dis ; 204 Suppl 3: S968-72, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21987777

RESUMO

The emergence of Reston ebolavirus (REBOV) in domestic swine in the Philippines has caused a renewed interest in REBOV pathogenicity. Here, the use of different rodent species as animal disease models for REBOV was investigated. BALB/c and STAT1(-)(/-) mice, Hartley guinea pigs, and Syrian hamsters were inoculated intraperitoneally with REBOV strain Pennsylvania or Reston08-A. Although virus replication occurred in guinea pigs, hamsters, and STAT1(-/-) mice, progression to disease was only observed in STAT1(-)(/-) mice. Moreover, REBOV Pennsylvania was more pathogenic than REBOV Reston08-A in this model. Thus, STAT1(-)(/-) mice may be used for research of REBOV pathogenicity and intervention strategies.


Assuntos
Modelos Animais de Doenças , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Animais , Cricetinae , Feminino , Cobaias , Fígado/virologia , Pulmão/virologia , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Baço/virologia , Fatores de Tempo , Viremia , Virulência
4.
J Virol ; 84(13): 6825-33, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20392847

RESUMO

The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, alpha2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to alpha2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with alpha2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.


Assuntos
Hemaglutininas Virais/metabolismo , Virus da Influenza A Subtipo H5N1/fisiologia , Receptores Virais/metabolismo , Ligação Viral , Replicação Viral , Substituição de Aminoácidos , Animais , Linhagem Celular , Furões , Hemaglutininas Virais/genética , Humanos , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza A Subtipo H3N2/fisiologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Mutação de Sentido Incorreto , Neuraminidase/genética , Neuraminidase/metabolismo , Mucosa Respiratória/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
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