Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus

Philpott, Matthew; Hioe, Catarina E.; Sheerar, Martha G.; Hinshaw, Virginia S.

doi:10.1128/jvi.64.6.2941-2947.1990

Cited by 62 publications

(51 citation statements)

References 31 publications

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“…The H5 HA gene of influenza virus A/Ty/Ont/7732/66 (H5N9) is known to elicit murine antibody and cytotoxic T-lymphocyte responses that can result in specific destruction of influenza virus-infected cells (28). Therefore, we inserted a fragment of the H5 HA gene (40) known to contain T-and B-cell antigenic sites (27) in place of the Hygr gene of GB102 to generate a vector designated GB112 (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…pGB112 was constructed by digestion of pGB109 with BssHII, treatment with the Klenow fragment, and addition of an EcoRI linker to generate the intermediate pGB111. Virginia S. Hinshaw, University of Wisconsin-Madison, provided an H5 HA gene fragment (nucleotides 1 to 1072 [40]) from influenza virus A/Ty/Ont/ 7732/66 (H5N9) which had been cloned into an SP64-based construct. This was digested with HindIll and treated with the Klenow fragment, and then an EcoRI linker was added.…”

Section: Methodsmentioning

confidence: 99%

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Human immunodeficiency virus vectors for inducible expression of foreign genes

Buchschacher

Panganiban

1992

J Virol

124

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Tat-dependent expression of an endogenous lethal or deleterious foreign gene might be useful for abrogating the production of human immunodeficiency virus (HIV) from cells. This type of HIV-induced cellular killing, as well as other approaches to gene therapy for HIV infection, would be facilitated by simple HIV vectors that express introduced genes in a Tat-inducible manner. As part of studies to examine the feasibility of this concept, we constructed HIV-1 vectors that express the hygromycin B phosphotransferase gene (Hygr) in a Tatdependent manner. Comparison of the efficiency of propagation of each vector indicates that sequences extending into the gag open reading frame are necessary in cis for efficient vector propagation. Southern blot analysis of genomic DNA isolated from vector-infected cells demonstrated that the vectors were capable of being propagated as expected without gross rearrangements or deletions. A fragment of the influenza A virus hemagglutinin (H5 HA) gene, capable of eliciting antibody and cytotoxic T-cell responses, was used as a marker for further characterization of the vector system. A Tat-dependent vector conferring the H5 HA' phenotype was assayed by indirect immunofluorescence, and cells which contained but did not express the H5 HA gene were isolated. The activation of H5 HA expression following HIV infection of Tat-cells that stably contained but did not express the H5 HA construct was determined to be an efficient process.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Human immunodeficiency virus vectors for inducible expression of foreign genes

Buchschacher

Panganiban

1992

J Virol

124

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“…Altered function or relevant site affected References HA1 Lung S128P None Antigenic site (position 133 in H3-numbering) Kaverin et al (2007Kaverin et al ( , 2002, Philpott et al (1990), and Stevens et al (2006) Inoculum K153R mutations/genome. Although this value is still rather high, it would lead to a fraction of e À7.0 $ 1 ‰ of genomes displaying no mutation and 3% of genomes with at most 2 mutations (Table 3) during the life time of infected chickens.…”

Section: Mutation Previously Reportedmentioning

confidence: 99%

Biased mutational pattern and quasispecies hypothesis in H5N1 virus

Gutiérrez

Viari

Godelle

et al. 2013

Infection, Genetics and Evolution

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Like other RNA viruses, influenza viruses are subject to high mutation rates. Carrying segmented RNA genomes, their genetic variability is even higher. We aimed at analyzing the mutational events occurring during the infection of chickens by the Highly Pathogenic Avian Influenza (HPAI) H5N1 virus. We therefore studied the different sequences of two surface proteins, hemagglutinin (HA) and neuraminidase (NA), as well as two internal proteins, PB2 and NS. Three organs (lung, spleen, brain) were obtained from a chicken, experimentally infected with a lethal dose of HPAI H5N1 virus. Cloning these PCR fragments enabled us to investigate the mutations undergone by the virus after several replicative cycles. The first outcome is the presence of a strong mutational bias, resembling host-driven ADAR1 adenosine deamination, which is responsible for 81% of all mutations. Whereas the frequency of RNA dependent RNA polymerase-related mutations is compatible with the survival of the virus, the ADAR1-like activity usually strongly increases the mutation frequency into a level of "error catastrophe" in theory incompatible with virus survival. Nevertheless, the virus was successfully infective. HPAI H5N1 virus displayed traits in agreement with the quasispecies theory. The role of this quasispecies structure in successful infection and the superposition with the ADAR1-like response is discussed.

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“…The HA of influenza virus is the major target for immune responses due to its role in mediating attachment to and penetration into host cells. The antigenic structure of HAs of H1, H2, H3, H5, and H9 subtypes of influenza A virus has been investigated by antigenic mapping and sequence analysis [2,11,12,24,26,28]. Antigenic mapping of an H1 HA, A/PR/8/34 (H1N1), indicates five immunodominant antigenic sites, designated Sa, Sb, Ca1, Ca2 and Cb [4], which are comparable to those of H3 subtype virus A/Hong Kong/1968 (H3N2), designated A, B, C, D and E [28].…”

Section: Introductionmentioning

confidence: 99%

Antigenic structure of the hemagglutinin of H9N2 influenza viruses

et al. 2008

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2 SummaryThe hemagglutinins (HAs) of H9 influenza viruses isolated from birds and mammals of different species were antigenically and genetically analyzed. Antigenic variants were selected from A/swine/Hong Kong/10/98 (H9N2) and A/duck/Hokkaido/13/00 (H9N2) in the presence of monoclonal antibodies (MAbs), respectively.Based on the reactivity patterns of these mutants with a panel of MAbs, at least 5 non-overlapping antigenic sites were defined using 8 MAbs which recognized 7 distinct epitopes on the H9 HA molecule. Based on the reactivity patterns with the panel of monoclonal antibodies, 21 H9N2 virus strains isolated from birds and mammals were divided into 7 antigenically distinct groups. The present findings indicate that it is important to monitor the antigenic variation in H9 influenza viruses. The panel of MAbs in the present study, thus, should be useful for detailed antigenic analysis of the H9 HAs for epidemiological studies, the selection of vaccine strains, and diagnosis.

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Hemagglutinin mutations related to attenuation and altered cell tropism of a virulent avian influenza A virus

Abstract: The H5 hemagglutinin (HA) of a highly virulent avian influenza virus, A/Turkey/Ontario/7732/66 (H5N9), was previously shown to have five neutralizing epitopes, and escape mutants within one epitope (group 1) were markedly attenuated (M.

Cited by 62 publications

References 31 publications

Human immunodeficiency virus vectors for inducible expression of foreign genes

Human immunodeficiency virus vectors for inducible expression of foreign genes

Biased mutational pattern and quasispecies hypothesis in H5N1 virus

Antigenic structure of the hemagglutinin of H9N2 influenza viruses

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