Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells
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...
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MDPI AG
2025-01-01
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| author | Gifty A. Mensah Anastasia Williams Pooja Khatkar Yuriy Kim James Erickson Alexandra Duverger Heather Branscome Kajal Patil Hafsa Chaudhry Yuntao Wu Olaf Kutsch Fatah Kashanchi |
| author_facet | Gifty A. Mensah Anastasia Williams Pooja Khatkar Yuriy Kim James Erickson Alexandra Duverger Heather Branscome Kajal Patil Hafsa Chaudhry Yuntao Wu Olaf Kutsch Fatah Kashanchi |
| author_sort | Gifty A. Mensah |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ec3b8723a6964c81ba0900f7eea49d06 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-ec3b8723a6964c81ba0900f7eea49d062025-01-24T13:26:44ZengMDPI AGCells2073-44092025-01-0114211910.3390/cells14020119Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander CellsGifty A. Mensah0Anastasia Williams1Pooja Khatkar2Yuriy Kim3James Erickson4Alexandra Duverger5Heather Branscome6Kajal Patil7Hafsa Chaudhry8Yuntao Wu9Olaf Kutsch10Fatah Kashanchi11Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USADepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USANational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USADepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USALaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USAAs 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.https://www.mdpi.com/2073-4409/14/2/119extracellular vesiclesHIV-1kinasescombined antiretroviral therapyCDK10GSK3β |
| spellingShingle | Gifty A. Mensah Anastasia Williams Pooja Khatkar Yuriy Kim James Erickson Alexandra Duverger Heather Branscome Kajal Patil Hafsa Chaudhry Yuntao Wu Olaf Kutsch Fatah Kashanchi Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells Cells extracellular vesicles HIV-1 kinases combined antiretroviral therapy CDK10 GSK3β |
| title | Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells |
| title_full | Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells |
| title_fullStr | Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells |
| title_full_unstemmed | Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells |
| title_short | Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells |
| title_sort | effect of kinases in extracellular vesicles from hiv 1 infected cells on bystander cells |
| topic | extracellular vesicles HIV-1 kinases combined antiretroviral therapy CDK10 GSK3β |
| url | https://www.mdpi.com/2073-4409/14/2/119 |
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