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Nef-induced differential gene expression in primary CD4+ T cells following infection with HIV-1 isolates

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Almost 80% of viral transcripts during early HIV-1 infection encode the Nef protein, which has been implicated in altering expression of a number of genes. In this study, we infected primary human CD4+ T cells with pseudotyped Nef-containing or Nef-deleted (Δ-nef) NL4-3 virus and used RNA-Sequencing (RNA-Seq) for transcriptomic analysis. Our results showed that the interferon response, IL-15 and JAK/STAT signaling, as well as genes involved in metabolism, apoptosis, cell cycle regulation, and ribosome biogenesis were all altered in the presence of Nef. These early Nef-mediated transcriptional alterations may play a role in priming the host cell for cellular activation and viral replication.

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Fig. 1

Data availability

Sequencing data can be found under BioSample Accession Numbers SAMN07676177 and SAMN07676178.


EGR 1:

Early growth response protein 1


Human immunodeficiency virus-1


Interferon stimulated gene 20 protein




Vesicular stomatitus virus G protein


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This project was supported in part by the RNA-Seq for the Next Generation Project, Cold Spring Harbor Laboratory DNA Learning Center (NSF-DUE #1323522); Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number UM1AI126617, with co-funding support from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations



RLF, AA, OOY, and DFN conceived and designed the experiments; AA and RLF performed the experiments; RLF, AA, OOY, and DFN analyzed the data; AA and OOY contributed reagents/materials/analysis tools; RLF and DFN wrote the paper.

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Correspondence to Robert L. Furler.

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The authors declare that they have no competing interests.

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Edited by Wolfram Gerlich.

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Furler, R.L., Ali, A., Yang, O.O. et al. Nef-induced differential gene expression in primary CD4+ T cells following infection with HIV-1 isolates. Virus Genes 55, 541–544 (2019).

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