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1.
Arch Virol ; 165(10): 2165-2176, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32740830

RESUMO

The PI3K/Akt signalling pathway is a crucial signalling cascade that regulates transcription, protein translation, cell growth, proliferation, cell survival, and metabolism. During viral infection, viruses exploit a variety of cellular pathways, including the well-known PI3K/Akt signalling pathway. Conversely, cells rely on this pathway to stimulate an antiviral response. The PI3K/Akt pathway is manipulated by a number of viruses, including DNA and RNA viruses and retroviruses. The aim of this review is to provide up-to-date information about the role of the PI3K-Akt pathway in infection with members of five different families of negative-sense ssRNA viruses. This pathway is hijacked for viral entry, regulation of endocytosis, suppression of premature apoptosis, viral protein expression, and replication. Although less common, the PI3K/Akt pathway can be downregulated as an immunomodulatory strategy or as a mechanism for inducing autophagy. Moreover, the cell activates this pathway as an antiviral strategy for interferon and cytokine production, among other strategies. Here, we present new data concerning the role of this pathway in infection with the paramyxovirus Newcastle disease virus (NDV). Our data seem to indicate that NDV uses the PI3K/Akt pathway to delay cell death and increase cell survival as a means of improving its replication. The interference of negative-sense ssRNA viruses with this essential pathway might have implications for the development of antiviral therapies.


Assuntos
Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Infecções por Vírus de RNA/genética , Apoptose/genética , Autofagia/genética , Autofagia/imunologia , Citocinas/genética , Citocinas/imunologia , Endocitose/genética , Endocitose/imunologia , Filoviridae/genética , Filoviridae/metabolismo , Filoviridae/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Interferons/genética , Interferons/imunologia , Orthomyxoviridae/genética , Orthomyxoviridae/metabolismo , Orthomyxoviridae/patogenicidade , Paramyxoviridae/genética , Paramyxoviridae/metabolismo , Paramyxoviridae/patogenicidade , Fosfatidilinositol 3-Quinase/imunologia , Pneumovirinae/genética , Pneumovirinae/metabolismo , Pneumovirinae/patogenicidade , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt/imunologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia , Rhabdoviridae/genética , Rhabdoviridae/metabolismo , Rhabdoviridae/patogenicidade , Transdução de Sinais , Proteínas Virais/genética , Proteínas Virais/imunologia , Internalização do Vírus , Replicação Viral
2.
J Virol ; 79(23): 14834-42, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16282483

RESUMO

The genomic structure and composition of an avian metapneumovirus (aMPV) recently isolated from wild Canada geese (goose 15a/01) in the United States, together with its replication, virulence, and immunogenicity in domestic turkeys, were investigated. The sizes of seven of the eight genes, sequence identity, and genome organization of goose aMPV were similar to those of turkey aMPV subtype C (aMPV/C) strains, indicating that it belonged to the subtype. However, the goose virus contained the largest attachment (G) gene of any pneumovirus or metapneumovirus, with the predicted G protein of 585 amino acids (aa) more than twice the sizes of G proteins from other subtype C viruses and human metapneumovirus and more than 170 aa larger than the G proteins from the other aMPV subtypes (subtypes A, B, and D). The large G gene resulted from a 1,015-nucleotide insertion at 18 nucleotides upstream of the termination signal of the turkey aMPV/C G gene. Three other aMPV isolates from Canada geese had similarly large G genes, whereas analysis of recent aMPV strains circulating in U.S. turkeys did not indicate the presence of the goose virus-like strain. In vitro, the goose virus replicated to levels (2 x 10(5) to 5 x 10(5) 50% tissue culture infective dose) comparable to those produced by turkey aMPV/C strains. More importantly, the virus replicated efficiently in the upper respiratory tract of domestic turkeys but with no clinical signs in either day-old or 2-week-old turkeys. The virus was also horizontally transmitted to naïve birds, and turkey infections with goose 15a/01 induced production of aMPV-specific antibodies. Challenging day-old or 2-week-old turkeys vaccinated with live goose aMPV resulted in lower clinical scores in 33% of the birds, whereas the rest of the birds had no detectable clinical signs of the upper respiratory disease, suggesting that the mutant virus may be a safe and effective vaccine against aMPV infection outbreaks in commercial turkeys.


Assuntos
Metapneumovirus/imunologia , Infecções por Paramyxoviridae/prevenção & controle , Infecções por Paramyxoviridae/veterinária , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Proteínas do Envelope Viral/imunologia , Vacinas Virais/administração & dosagem , Animais , Sequência de Bases , Metapneumovirus/genética , Metapneumovirus/metabolismo , Dados de Sequência Molecular , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Pneumovirinae/genética , Pneumovirinae/imunologia , Pneumovirinae/metabolismo , Pneumovirinae/patogenicidade , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/virologia , Perus , Proteínas do Envelope Viral/química
4.
J Clin Microbiol ; 41(4): 1730-5, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12682171

RESUMO

A serologically distinct avian metapneumovirus (aMPV) was isolated in the United States after an outbreak of turkey rhinotracheitis (TRT) in February 1997. The newly recognized U.S. virus was subsequently demonstrated to be genetically distinct from European subtypes and was designated aMPV serotype C (aMPV/C). We have determined the nucleotide sequence of the gene encoding the cell attachment glycoprotein (G) of aMPV/C (Colorado strain and three Minnesota isolates) and predicted amino acid sequence by sequencing cloned cDNAs synthesized from intracellular RNA of aMPV/C-infected cells. The nucleotide sequence comprised 1,321 nucleotides with only one predicted open reading frame encoding a protein of 435 amino acids, with a predicted M(r) of 48,840. The structural characteristics of the predicted G protein of aMPV/C were similar to those of the human respiratory syncytial virus (hRSV) attachment G protein, including two mucin-like regions (heparin-binding domains) flanking both sides of a CX3C chemokine motif present in a conserved hydrophobic pocket. Comparison of the deduced G-protein amino acid sequence of aMPV/C with those of aMPV serotypes A, B, and D, as well as hRSV revealed overall predicted amino acid sequence identities ranging from 4 to 16.5%, suggesting a distant relationship. However, G-protein sequence identities ranged from 72 to 97% when aMPV/C was compared to other members within the aMPV/C subtype or 21% for the recently identified human MPV (hMPV) G protein. Ratios of nonsynonymous to synonymous nucleotide changes were greater than one in the G gene when comparing the more recent Minnesota isolates to the original Colorado isolate. Epidemiologically, this indicates positive selection among U.S. isolates since the first outbreak of TRT in the United States.


Assuntos
Metapneumovirus/metabolismo , Epidemiologia Molecular , Infecções por Paramyxoviridae/veterinária , Filogenia , Doenças das Aves Domésticas/epidemiologia , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Chlorocebus aethiops , Humanos , Metapneumovirus/química , Metapneumovirus/genética , Dados de Sequência Molecular , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Pneumovirinae/química , Pneumovirinae/genética , Pneumovirinae/metabolismo , Doenças das Aves Domésticas/microbiologia , Perus/virologia , Estados Unidos/epidemiologia , Células Vero , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
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