Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

ABSTRACT B cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4+ cells in HIV infection. It is assumed that CD8+ T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8+ T cell entry. Here we ana...

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Autores principales:	Sonja Windmann, Lucas Otto, Camilla Patrizia Hrycak, Anna Malyshkina, Nadine Bongard, Paul David, Matthias Gunzer, Ulf Dittmer, Wibke Bayer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	follicular B cells murine leukemia virus persistence retroviruses viral immunity viral pathogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c3c4eee29d0d4f0e9177badd16b69523
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spelling	oai:doaj.org-article:c3c4eee29d0d4f0e9177badd16b695232021-11-15T15:55:13ZInfection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence10.1128/mBio.00004-192150-7511https://doaj.org/article/c3c4eee29d0d4f0e9177badd16b695232019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00004-19https://doaj.org/toc/2150-7511ABSTRACT B cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4+ cells in HIV infection. It is assumed that CD8+ T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8+ T cell entry. Here we analyzed the infected cell population in the Friend retrovirus (FV) infection and investigated whether FV can similarly infect follicular cells. For analysis of FV-infected cells, we constructed a recombinant FV encoding the bright fluorescent protein mWasabi and performed flow cytometry with cells isolated from spleens, lymph nodes and bone marrow of FV-mWasabi-infected mice. Using t-stochastic neighbor embedding for data exploration, we demonstrate how the target cell population changes during the course of infection. While FV was widely distributed in erythrocytes, myeloid cells, B cells, and CD4+ T cells in the acute phase of infection, the bulk viral load in the late phase was carried by macrophages and follicular B and CD4+ T cells, suggesting that FV persists in cells that are protected from CD8+ T cell killing. Importantly, seeding into follicular cells was equally observed in CD8+ T cell-depleted mice and in highly FV-susceptible mice that mount a very weak immune response, demonstrating that infection of follicular cells is not driven by immune pressure. Our data demonstrate that infection of cells in the B cell follicle is a characteristic of the FV infection, making this murine retrovirus an even more valuable model for development of retrovirus immunotherapy approaches. IMPORTANCE Human immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.Sonja WindmannLucas OttoCamilla Patrizia HrycakAnna MalyshkinaNadine BongardPaul DavidMatthias GunzerUlf DittmerWibke BayerAmerican Society for Microbiologyarticlefollicular B cellsmurine leukemia viruspersistenceretrovirusesviral immunityviral pathogenesisMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	follicular B cells murine leukemia virus persistence retroviruses viral immunity viral pathogenesis Microbiology QR1-502
spellingShingle	follicular B cells murine leukemia virus persistence retroviruses viral immunity viral pathogenesis Microbiology QR1-502 Sonja Windmann Lucas Otto Camilla Patrizia Hrycak Anna Malyshkina Nadine Bongard Paul David Matthias Gunzer Ulf Dittmer Wibke Bayer Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
description	ABSTRACT B cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4+ cells in HIV infection. It is assumed that CD8+ T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8+ T cell entry. Here we analyzed the infected cell population in the Friend retrovirus (FV) infection and investigated whether FV can similarly infect follicular cells. For analysis of FV-infected cells, we constructed a recombinant FV encoding the bright fluorescent protein mWasabi and performed flow cytometry with cells isolated from spleens, lymph nodes and bone marrow of FV-mWasabi-infected mice. Using t-stochastic neighbor embedding for data exploration, we demonstrate how the target cell population changes during the course of infection. While FV was widely distributed in erythrocytes, myeloid cells, B cells, and CD4+ T cells in the acute phase of infection, the bulk viral load in the late phase was carried by macrophages and follicular B and CD4+ T cells, suggesting that FV persists in cells that are protected from CD8+ T cell killing. Importantly, seeding into follicular cells was equally observed in CD8+ T cell-depleted mice and in highly FV-susceptible mice that mount a very weak immune response, demonstrating that infection of follicular cells is not driven by immune pressure. Our data demonstrate that infection of cells in the B cell follicle is a characteristic of the FV infection, making this murine retrovirus an even more valuable model for development of retrovirus immunotherapy approaches. IMPORTANCE Human immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.
format	article
author	Sonja Windmann Lucas Otto Camilla Patrizia Hrycak Anna Malyshkina Nadine Bongard Paul David Matthias Gunzer Ulf Dittmer Wibke Bayer
author_facet	Sonja Windmann Lucas Otto Camilla Patrizia Hrycak Anna Malyshkina Nadine Bongard Paul David Matthias Gunzer Ulf Dittmer Wibke Bayer
author_sort	Sonja Windmann
title	Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
title_short	Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
title_full	Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
title_fullStr	Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
title_full_unstemmed	Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence
title_sort	infection of b cell follicle-resident cells by friend retrovirus occurs during acute infection and is maintained during viral persistence
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/c3c4eee29d0d4f0e9177badd16b69523
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Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

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