Oncotarget

Research Papers:

Impact of exosomal HIV-1 Tat expression on the human cellular proteome

Huafei Lu, Xiaoli Tang, Mitchell Sibley, Jillian Coburn, R. Shyama Prasad Rao, Nagib Ahsan _ and Bharat Ramratnam _

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Oncotarget. 2019; 10:5632-5644. https://doi.org/10.18632/oncotarget.27207

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Abstract

Huafei Lu1, Xiaoli Tang1, Mitchell Sibley1, Jillian Coburn2, R. Shyama Prasad Rao3, Nagib Ahsan2,4 and Bharat Ramratnam1,2,5

1 Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

2 COBRE Center for Cancer Research Development, Proteomics Core Facility, Rhode Island Hospital, Providence, RI 02903, USA

3 Biostatistics and Bioinformatics Division, Yenepoya Research Center, Yenepoya University, Mangalore 575018, India

4 Division of Biology and Medicine, Brown University, Providence, RI 02903, USA

5 Clinical Research Center of Lifespan, Providence, RI 02903, USA

Correspondence to:

Nagib Ahsan,email: nagib_ahsan@brown.edu,
nagib.ahsan@lifespan.org
Bharat Ramratnam,email: BRamratnam@lifespan.org

Keywords: HIV-1; tat protein; exosome; label-free proteomics; ROS

Received: April 11, 2019     Accepted: August 27, 2019     Published: September 24, 2019

ABSTRACT

HIV-1 exists in a latent form in all infected patients. When antiretroviral therapy is stopped, viral replication resumes. The HIV-1 Tat protein is a potent activator of viral transcription. Our previous work has demonstrated that exosomal formulations of Tat can reverse HIV-1 latency in primary CD4+ T lymphocytes isolated from long term antiretroviral treated individuals suggesting a potential role for Tat as a therapeutic HIV-1 Latency Reversal Agent (LRA). Here, we employed the label-free proteomic approach for profiling the proteomic changes associated with exosomal Tat production in human cell lines. Comparative proteomic analysis revealed that >30% peptides were differentially expressed in abundance in the Tat-expressing cell line compared with relevant controls. As expected, many of the known Tat-interactor proteins were upregulated. Tat expression also led to the upregulation of antioxidant proteins suggesting Tat-mediates an oxidative burst. Gene ontology and pathway analyses of these differentially expressed proteins showed enrichment of extracellular vesicular exosome and spliceosome localized proteins and proteins involved with transcriptional and translational mechanisms. Our work suggests that HIV-1 Tat expression leads to perturbations in cellular protein expression. In vivo administration of Tat using HIV/SIV animal models needs to be performed to assess the physiologic significance of Tat-induced proteomic changes prior to developing HIV-1 Tat as an LRA.


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