Full Text

Turn on search term navigation

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

As of 2023, there were 39.9 million people living with Human Immunodeficiency Virus type 1 (HIV-1). Although great strides have been made in treatment options for HIV-1, and our understanding of the HIV-1 life cycle has vastly improved since the start of this global health crisis, a functional cure remains elusive. One of the main barriers to a cure is latency, which allows the virus to persist despite combined antiretroviral therapy (cART). Recently, we have found that exosomes, which are small, membrane-enclosed particles released by virtually all cell types and known to mediate intercellular communication, caused an increase in RNA Polymerase II loading onto the HIV-1 promoter. This resulted in the production of both short- and long-length viral transcripts in infected cells under cART. This current study examines the effects of exosome-associated kinases on bystander cells. The phospho-kinase profiling of exosomes revealed differences in the kinase payload of exosomes derived from uninfected and HIV-1-infected cells, with CDK10, GSK3β, and MAPK8 having the largest concentration differences. These kinases were shown to be biologically active and capable of phosphorylating substrates, and they modulated changes in the cell cycle dynamics of exposed cells. Given the relevance of such effects for the immune response, our results implicate exosome-associated kinases as new possible key contributors to HIV-1 pathogenesis that affect bystander cells. These findings may guide new therapeutic avenues to improve the current antiretroviral treatment regimens.

Details

Title
Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells
Author
Mensah, Gifty A 1 ; Williams, Anastasia 1   VIAFID ORCID Logo  ; Khatkar, Pooja 1   VIAFID ORCID Logo  ; Kim, Yuriy 1   VIAFID ORCID Logo  ; Erickson, James 1 ; Duverger, Alexandra 2   VIAFID ORCID Logo  ; Branscome, Heather 1 ; Patil, Kajal 1 ; Chaudhry, Hafsa 1 ; Wu, Yuntao 3 ; Kutsch, Olaf 2 ; Kashanchi, Fatah 1   VIAFID ORCID Logo 

 Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA; [email protected] (G.A.M.); [email protected] (A.W.); [email protected] (P.K.); [email protected] (Y.K.); [email protected] (J.E.); [email protected] (H.B.); [email protected] (K.P.); [email protected] (H.C.) 
 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] (A.D.); [email protected] (O.K.) 
 National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA; [email protected] 
First page
119
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
20734409
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3159390236
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.