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HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells

Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the...

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Autores principales: Crisci, Elisa, Svanberg, Cecilia, Ellegård, Rada, Khalid, Mohammad, Hellblom, Julia, Okuyama, Kazuki, Bhattacharya, Pradyot, Nyström, Sofia, Shankar, Esaki M., Eriksson, Kristina, Larsson, Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909011/
https://www.ncbi.nlm.nih.gov/pubmed/31867020
http://dx.doi.org/10.3389/fimmu.2019.02889
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author Crisci, Elisa
Svanberg, Cecilia
Ellegård, Rada
Khalid, Mohammad
Hellblom, Julia
Okuyama, Kazuki
Bhattacharya, Pradyot
Nyström, Sofia
Shankar, Esaki M.
Eriksson, Kristina
Larsson, Marie
author_facet Crisci, Elisa
Svanberg, Cecilia
Ellegård, Rada
Khalid, Mohammad
Hellblom, Julia
Okuyama, Kazuki
Bhattacharya, Pradyot
Nyström, Sofia
Shankar, Esaki M.
Eriksson, Kristina
Larsson, Marie
author_sort Crisci, Elisa
collection PubMed
description Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the first innate cell types that encounter HIV-1 and HSV-2 in the genital mucosa. HSV-2 infection has been shown to modulate DCs, rendering them more receptive to HIV infection. Here, we investigated the potential mechanisms underlying HSV-2-mediated augmentation of HIV-1 infection. We demonstrated that the presence of HSV-2 enhanced productive HIV-1 infection of DCs and boosted inflammatory and antiviral responses. The HSV-2 augmented HIV-1 infection required intact HSV-2 DNA, but not active HSV-2 DNA replication. Furthermore, the augmented HIV infection of DCs involved the cGAS-STING pathway. Interestingly, we could not see any involvement of TLR2 or TLR3 nor suppression of infection by IFN-β production. The conditioning by HSV-2 in dual exposed DCs decreased protein expression of IFI16, cGAS, STING, and TBK1, which is associated with signaling through the STING pathway. Dual exposure to HSV-2 and HIV-1 gave decreased levels of several HIV-1 restriction factors, especially SAMHD1, TREX1, and APOBEC3G. Activation of the STING pathway in DCs by exposure to both HSV-2 and HIV-1 most likely led to the proteolytic degradation of the HIV-1 restriction factors SAMHD1, TREX1, and APOBEC3G, which should release their normal restriction of HIV infection in DCs. This released their normal restriction of HIV infection in DCs. We showed that HSV-2 reprogramming of cellular signaling pathways and protein expression levels in the DCs provided a setting where HIV-1 can establish a higher productive infection in the DCs. In conclusion, HSV-2 reprogramming opens up DCs for HIV-1 infection and creates a microenvironment favoring HIV-1 transmission.
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spelling pubmed-69090112019-12-20 HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells Crisci, Elisa Svanberg, Cecilia Ellegård, Rada Khalid, Mohammad Hellblom, Julia Okuyama, Kazuki Bhattacharya, Pradyot Nyström, Sofia Shankar, Esaki M. Eriksson, Kristina Larsson, Marie Front Immunol Immunology Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the first innate cell types that encounter HIV-1 and HSV-2 in the genital mucosa. HSV-2 infection has been shown to modulate DCs, rendering them more receptive to HIV infection. Here, we investigated the potential mechanisms underlying HSV-2-mediated augmentation of HIV-1 infection. We demonstrated that the presence of HSV-2 enhanced productive HIV-1 infection of DCs and boosted inflammatory and antiviral responses. The HSV-2 augmented HIV-1 infection required intact HSV-2 DNA, but not active HSV-2 DNA replication. Furthermore, the augmented HIV infection of DCs involved the cGAS-STING pathway. Interestingly, we could not see any involvement of TLR2 or TLR3 nor suppression of infection by IFN-β production. The conditioning by HSV-2 in dual exposed DCs decreased protein expression of IFI16, cGAS, STING, and TBK1, which is associated with signaling through the STING pathway. Dual exposure to HSV-2 and HIV-1 gave decreased levels of several HIV-1 restriction factors, especially SAMHD1, TREX1, and APOBEC3G. Activation of the STING pathway in DCs by exposure to both HSV-2 and HIV-1 most likely led to the proteolytic degradation of the HIV-1 restriction factors SAMHD1, TREX1, and APOBEC3G, which should release their normal restriction of HIV infection in DCs. This released their normal restriction of HIV infection in DCs. We showed that HSV-2 reprogramming of cellular signaling pathways and protein expression levels in the DCs provided a setting where HIV-1 can establish a higher productive infection in the DCs. In conclusion, HSV-2 reprogramming opens up DCs for HIV-1 infection and creates a microenvironment favoring HIV-1 transmission. Frontiers Media S.A. 2019-12-06 /pmc/articles/PMC6909011/ /pubmed/31867020 http://dx.doi.org/10.3389/fimmu.2019.02889 Text en Copyright © 2019 Crisci, Svanberg, Ellegård, Khalid, Hellblom, Okuyama, Bhattacharya, Nyström, Shankar, Eriksson and Larsson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Crisci, Elisa
Svanberg, Cecilia
Ellegård, Rada
Khalid, Mohammad
Hellblom, Julia
Okuyama, Kazuki
Bhattacharya, Pradyot
Nyström, Sofia
Shankar, Esaki M.
Eriksson, Kristina
Larsson, Marie
HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title_full HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title_fullStr HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title_full_unstemmed HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title_short HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
title_sort hsv-2 cellular programming enables productive hiv infection in dendritic cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909011/
https://www.ncbi.nlm.nih.gov/pubmed/31867020
http://dx.doi.org/10.3389/fimmu.2019.02889
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