Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells

ABSTRACT Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggest...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D. Scharff
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	AID AIDS B cell HIV Tat somatic hypermutation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b0a442bfc9924af8849b9674fcf5263a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b0a442bfc9924af8849b9674fcf5263a
record_format	dspace
spelling	oai:doaj.org-article:b0a442bfc9924af8849b9674fcf5263a2021-11-15T15:53:27ZHuman Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells10.1128/mBio.02315-172150-7511https://doaj.org/article/b0a442bfc9924af8849b9674fcf5263a2018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02315-17https://doaj.org/toc/2150-7511ABSTRACT Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined. Here, we demonstrate that the cell membrane-permeable HIV Tat proteins enhance activation-induced deaminase (AID)-mediated somatic hypermutation (SHM) of antibody V regions through their modulation of the endogenous polymerase II (Pol II) transcriptional process. Extremely small amounts of Tat that could come from bystander HIV-infected cells were sufficient to promote SHM. Our data suggest HIV Tat is one missing link between HIV infection and the overall B cell genomic instability in AIDS patients. IMPORTANCE Although the introduction of antiretroviral therapy (ART) has successfully controlled primary effects of human immunodeficiency virus (HIV) infection, such as HIV proliferation and HIV-induced immune deficiency, it did not eliminate the increased susceptibility of HIV-infected patients to B cell lymphomas. We find that a secreted HIV protein, Tat, enhances the intrinsic antibody diversification mechanism by increasing the AID-induced somatic mutations at the heavy-chain variable (VH) regions in human B cells. This could contribute to the high rate of mutation in the variable regions of broadly neutralizing anti-HIV antibodies and the genomewide mutations leading to B cell malignancies in HIV carriers.Xiaohua WangZhi DuanGuojun YuManxia FanMatthew D. ScharffAmerican Society for MicrobiologyarticleAIDAIDSB cellHIVTatsomatic hypermutationMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	AID AIDS B cell HIV Tat somatic hypermutation Microbiology QR1-502
spellingShingle	AID AIDS B cell HIV Tat somatic hypermutation Microbiology QR1-502 Xiaohua Wang Zhi Duan Guojun Yu Manxia Fan Matthew D. Scharff Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
description	ABSTRACT Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined. Here, we demonstrate that the cell membrane-permeable HIV Tat proteins enhance activation-induced deaminase (AID)-mediated somatic hypermutation (SHM) of antibody V regions through their modulation of the endogenous polymerase II (Pol II) transcriptional process. Extremely small amounts of Tat that could come from bystander HIV-infected cells were sufficient to promote SHM. Our data suggest HIV Tat is one missing link between HIV infection and the overall B cell genomic instability in AIDS patients. IMPORTANCE Although the introduction of antiretroviral therapy (ART) has successfully controlled primary effects of human immunodeficiency virus (HIV) infection, such as HIV proliferation and HIV-induced immune deficiency, it did not eliminate the increased susceptibility of HIV-infected patients to B cell lymphomas. We find that a secreted HIV protein, Tat, enhances the intrinsic antibody diversification mechanism by increasing the AID-induced somatic mutations at the heavy-chain variable (VH) regions in human B cells. This could contribute to the high rate of mutation in the variable regions of broadly neutralizing anti-HIV antibodies and the genomewide mutations leading to B cell malignancies in HIV carriers.
format	article
author	Xiaohua Wang Zhi Duan Guojun Yu Manxia Fan Matthew D. Scharff
author_facet	Xiaohua Wang Zhi Duan Guojun Yu Manxia Fan Matthew D. Scharff
author_sort	Xiaohua Wang
title	Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
title_short	Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
title_full	Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
title_fullStr	Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
title_full_unstemmed	Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
title_sort	human immunodeficiency virus tat protein aids v region somatic hypermutation in human b cells
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/b0a442bfc9924af8849b9674fcf5263a
work_keys_str_mv	AT xiaohuawang humanimmunodeficiencyvirustatproteinaidsvregionsomatichypermutationinhumanbcells AT zhiduan humanimmunodeficiencyvirustatproteinaidsvregionsomatichypermutationinhumanbcells AT guojunyu humanimmunodeficiencyvirustatproteinaidsvregionsomatichypermutationinhumanbcells AT manxiafan humanimmunodeficiencyvirustatproteinaidsvregionsomatichypermutationinhumanbcells AT matthewdscharff humanimmunodeficiencyvirustatproteinaidsvregionsomatichypermutationinhumanbcells
_version_	1718427237908217856

Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells

Ejemplares similares