Dataset Information

Comparative analysis of differential cellular genome and proteome regulation by HIV-1 and HIV-2 pseudovirions in the early phase of infection

ABSTRACT: Beside the similar structure and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking difference exist between the in terms of replication dynamics and clinical manifestation of infection. Although pathomechanism of HIV-1 infection well characterized, relatively few data are available regarding HIV-2 viral replication, and its interaction with host cell protein during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1 / 2 pseudovirions during eight, 12, and 26 hour time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points, suggest a more diverse, yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on the cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or keratinocyte differentiation. Proteomics analysis revealed that HIV-1 upregulated, while HIV-2 downregulated proteins involved viral protein expression and replication. Our study provides an insight into the understudied replication cycle of HIV-2, and enrich our knowledge about the use of HIV-based lentiviral vectors in general.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Human Immunodeficiency Virus 2 (ncbitaxon:11709) Human Immunodeficiency Virus 1 (ncbitaxon:11676)

SUBMITTER: Gergo Kallo

PROVIDER: MSV000092581 | MassIVE | Thu Aug 03 04:12:00 BST 2023

SECONDARY ACCESSION(S): PXD044317

REPOSITORIES: MassIVE

ACCESS DATA

Publications

Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection.

Linkner Tamás Richárd TR Ambrus Viktor V Kunkli Balázs B Szojka Zsófia Ilona ZI Kalló Gergő G Csősz Éva É Kumar Ajneesh A Emri Miklós M Tőzsér József J Mahdi Mohamed M

International journal of molecular sciences 20231227 1

In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host-cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyse ...[more]

PMID: 38203551

Similar Datasets

Project description:During HIV-1 infection, there is a massive perturbation of host gene expression, but as yet, genome-wide studies have not identified host genes affecting HIV-1 replication in lymphatic tissue, the primary site of virus-host interactions. In this study, we isolated RNA from the inguinal lymph nodes of 22 HIV-1-infected individuals and utilized a microarray approach to identify host genes critically important for viral replication in lymphatic tissue by examining gene expression associated with viral load. Strikingly, ~95% of the transcripts (558) in this data set (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset (1) inhibit cellular activation/proliferation (ex.: TCFL5, SOCS5 and SCOS7, KLF10), (2) promote heterochromatin formation (ex.: HIC2, CREBZF, ZNF148/ZBP-89), (3) increase collagen synthesis (ex.: PLOD2, POSTN, CRTAP), and (4) reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified (ex.: NR3C1, HNRNPU, PACT). Only ~5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all these genes function in innate and adaptive immunity, particularly highlighting a heightened interferon system. The predominance of negative correlations as well as the disconnect between host defenses and viral load point to the importance of genes that regulate target cell activation and genes that code for potentially new restriction factors as determinants of viral load rather than conventional host defenses. Total RNA was isolated from the inguinal lymph nodes of 22 HIV-1-infected subjects at different clinical stages (and varying viral loads) and prepared for RNA extraction and hybridization on Affymetrix Human Genome U133 Plus 2.0 microarrays. Replicate arrays were performed for lymph node samples to minimize assay noise and host genes critically important for viral replication in lymphatic tissue were identified by examining gene expression and its association with viral load. Replicates were not performed for samples WB91 and TS35 due to limited amounts of biomaterial.

Dataset Information

Comparative analysis of differential cellular genome and proteome regulation by HIV-1 and HIV-2 pseudovirions in the early phase of infection

Publications

Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure