Dataset Information

Dynamics of Proteo-Transcriptomic Response to HIV-1 Infection

ABSTRACT: We have investigated the dynamic host response to HIV-1 infection by systematically measuring transcriptome, proteome and phosphoproteome expression changes in infected and uninfected SupT1 CD4+ T cells at 5 time-points throughout the HIV-1 replication cycle (from 2h to 24h).

OTHER RELATED OMICS DATASETS IN: GSE100587

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human) Human Immunodeficiency Virus Type 1 3916-cro

TISSUE(S): T Cell, Cell Culture

DISEASE(S): Human Immunodeficiency Virus Infectious Disease

SUBMITTER: Manfredo Quadroni

LAB HEAD: Manfredo Quadroni

PROVIDER: PXD005810 | Pride | 2019-01-22

REPOSITORIES: Pride

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Publications

Proteo-Transcriptomic Dynamics of Cellular Response to HIV-1 Infection.

Golumbeanu Monica M Desfarges Sébastien S Hernandez Céline C Quadroni Manfredo M Rato Sylvie S Mohammadi Pejman P Telenti Amalio A Beerenwinkel Niko N Ciuffi Angela A

Scientific reports 20190118 1

Throughout the HIV-1 replication cycle, complex host-pathogen interactions take place in the infected cell, leading to the production of new virions. The virus modulates the host cellular machinery in order to support its life cycle, while counteracting intracellular defense mechanisms. We investigated the dynamic host response to HIV-1 infection by systematically measuring transcriptomic, proteomic, and phosphoproteomic expression changes in infected and uninfected SupT1 CD4+ T cells at five ti ...[more]

PMID: 30659199

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Project description:Attenuated poxviruses are safe and capable to express foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and direct and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. RNA expression obtained from DCs infected by NYVAC-C-dB19R and NYVAC-C-KC-dB19R compared to RNA expression obtained from DCs infected by NYVAC-C Supplementary file 'normalized_data_Human_V3_V2.txt' reports data for ILMN identifiers common to platforms HumanRef8V2 and HumanRef8V3.

Dataset Information

Dynamics of Proteo-Transcriptomic Response to HIV-1 Infection

Publications

Proteo-Transcriptomic Dynamics of Cellular Response to HIV-1 Infection.

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