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Article ; Online: Subsets of Tissue CD4 T Cells Display Different Susceptibilities to HIV Infection and Death: Analysis by CyTOF and Single Cell RNA-seq.

Luo, Xiaoyu / Frouard, Julie / Zhang, Gang / Neidleman, Jason / Xie, Guorui / Sheedy, Emma / Roan, Nadia R / Greene, Warner C

Frontiers in immunology

2022 Volume 13, Page(s) 883420

Abstract: CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell ... ...

Abstract	CD4 T lymphocytes belong to diverse cellular subsets whose sensitivity or resistance to HIV-associated killing remains to be defined. Working with lymphoid cells from human tonsils, we characterized the HIV-associated depletion of various CD4 T cell subsets using mass cytometry and single-cell RNA-seq. CD4 T cell subsets preferentially killed by HIV are phenotypically distinct from those resistant to HIV-associated cell death, in a manner not fully accounted for by their susceptibility to productive infection. Preferentially-killed subsets express CXCR5 and CXCR4 while preferentially-infected subsets exhibit an activated and exhausted effector memory cell phenotype. Single-cell RNA-seq analysis reveals that the subsets of preferentially-killed cells express genes favoring abortive infection and pyroptosis. These studies emphasize a complex interplay between HIV and distinct tissue-based CD4 T cell subsets, and the important contribution of abortive infection and inflammatory programmed cell death to the overall depletion of CD4 T cells that accompanies untreated HIV infection.
MeSH term(s)	CD4-Positive T-Lymphocytes ; HIV Infections ; HIV-1/physiology ; Humans ; RNA-Seq ; T-Lymphocyte Subsets
Language	English
Publishing date	2022-06-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.883420
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: HIV-1 Replication Benefits from the RNA Epitranscriptomic Code.

Kong, Weili / Rivera-Serrano, Efraín E / Neidleman, Jason A / Zhu, Jian

Journal of molecular biology

2019 Volume 431, Issue 24, Page(s) 5032–5038

Abstract: The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and 5-methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA ... ...

Abstract	The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and 5-methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA methylations through distinct mechanisms. In this review, we summarize the recent advances in this emerging field and discuss the role of RNA methylation writers and readers in HIV-1 infection, which may help to find alternative strategies to control HIV-1 infection.
MeSH term(s)	Epigenesis, Genetic ; Gene Expression Regulation, Viral ; HIV Infections/virology ; HIV-1/physiology ; Humans ; Methylation ; Models, Biological ; RNA, Viral ; Transcription, Genetic ; Virus Replication
Chemical Substances	RNA, Viral
Language	English
Publishing date	2019-10-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2019.09.021
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Article ; Online: Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4

Xie, Guorui / Luo, Xiaoyu / Ma, Tongcui / Frouard, Julie / Neidleman, Jason / Hoh, Rebecca / Deeks, Steven G / Greene, Warner C / Roan, Nadia R

Cell reports

2021 Volume 35, Issue 4, Page(s) 109038

Abstract: Relatively little is known about features of T cells targeted by HIV in vivo. By applying bioinformatics analysis to mass cytometry (CyTOF)-phenotyped specimens from individuals with viremia and in-vitro-infected cells from uninfected donors, we provide ... ...

Abstract	Relatively little is known about features of T cells targeted by HIV in vivo. By applying bioinformatics analysis to mass cytometry (CyTOF)-phenotyped specimens from individuals with viremia and in-vitro-infected cells from uninfected donors, we provide an atlas of the phenotypes of in vivo and in vitro HIV-susceptible cells. T helper 17 (Th17) and α4β1
MeSH term(s)	CD4-Positive T-Lymphocytes/metabolism ; HIV-1/genetics ; Humans ; Immunologic Memory/genetics ; T-Lymphocyte Subsets/metabolism
Language	English
Publishing date	2021-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109038
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Article: mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status.

Neidleman, Jason / Luo, Xiaoyu / McGregor, Matthew / Xie, Guorui / Murray, Victoria / Greene, Warner C / Lee, Sulggi A / Roan, Nadia R

bioRxiv : the preprint server for biology

2021

Abstract: While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, ...

Abstract	While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.05.12.443888
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Article ; Online: mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status.

Neidleman, Jason / Luo, Xiaoyu / McGregor, Matthew / Xie, Guorui / Murray, Victoria / Greene, Warner C / Lee, Sulggi A / Roan, Nadia R

eLife

2021 Volume 10

Abstract	While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.
MeSH term(s)	Adult ; Aged ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/pharmacology ; Female ; Humans ; Immunization, Secondary ; Longitudinal Studies ; Male ; Middle Aged ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/drug effects ; Vaccination ; Vaccines, Synthetic/pharmacology ; Young Adult ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-10-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.72619
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: HIV-1 Fusion Assay.

Cavrois, Marielle / Neidleman, Jason / Greene, Warner C

Bio-protocol

2016 Volume 4, Issue 16

Abstract: The HIV-1 fusion assay measures all steps in the HIV-1 life cycle up to and including viral fusion. It relies on the incorporation of a β-lactamase Vpr (BlaM-Vpr) protein chimera into the virion and the subsequent transfer of this chimera into the target ...

Abstract	The HIV-1 fusion assay measures all steps in the HIV-1 life cycle up to and including viral fusion. It relies on the incorporation of a β-lactamase Vpr (BlaM-Vpr) protein chimera into the virion and the subsequent transfer of this chimera into the target cell by fusion (Figure 1). The transfer is monitored by the enzymatic cleavage of CCF2, a fluorescent dye substrate of β-lactamase, loaded into the target cells. Cleavage of the β-lactam ring in CCF2 by β-lactamase changes the fluorescence emission spectrum of the dye from green (520 nm) to blue (447 nm). This change reflects virion fusion and can be detected by flow cytometry (Figure 2).
Language	English
Publishing date	2016-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325
ISSN	2331-8325
DOI	10.21769/bioprotoc.1212
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Article ; Online: Female Genital Fibroblasts Diminish the In Vitro Efficacy of PrEP against HIV.

George, Ashley F / McGregor, Matthew / Gingrich, David / Neidleman, Jason / Marquez, Rebecca S / Young, Kyrlia C / Thanigaivelan, Kaavya L / Greene, Warner C / Tien, Phyllis C / Deitchman, Amelia N / Spitzer, Trimble L / Roan, Nadia R

Viruses

2022 Volume 14, Issue 8

Abstract: The efficacy of HIV pre-exposure prophylaxis (PrEP) is high in men who have sex with men, but much more variable in women, in a manner largely attributed to low adherence. This reduced efficacy, however, could also reflect biological factors. ... ...

Abstract	The efficacy of HIV pre-exposure prophylaxis (PrEP) is high in men who have sex with men, but much more variable in women, in a manner largely attributed to low adherence. This reduced efficacy, however, could also reflect biological factors. Transmission to women is typically via the female reproductive tract (FRT), and vaginal dysbiosis, genital inflammation, and other factors specific to the FRT mucosa can all increase transmission risk. We have demonstrated that mucosal fibroblasts from the lower and upper FRT can markedly enhance HIV infection of CD4+ T cells. Given the current testing of tenofovir disoproxil fumarate, cabotegravir, and dapivirine regimens as candidate PrEP agents for women, we set out to determine using in vitro assays whether endometrial stromal fibroblasts (eSF) isolated from the FRT can affect the anti-HIV activity of these PrEP drugs. We found that PrEP drugs exhibit significantly reduced antiviral efficacy in the presence of eSFs, not because of decreased PrEP drug availability, but rather of eSF-mediated enhancement of HIV infection. These findings suggest that drug combinations that target both the virus and infection-promoting factors in the FRT-such as mucosal fibroblasts-may be more effective than PrEP alone at preventing sexual transmission of HIV to women.
MeSH term(s)	Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Female ; Fibroblasts ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; Homosexuality, Male ; Humans ; Male ; Sexual and Gender Minorities ; Vagina
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081723
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Article ; Online: Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals.

George, Ashley F / Luo, Xiaoyu / Neidleman, Jason / Hoh, Rebecca / Vohra, Poonam / Thomas, Reuben / Shin, Min-Gyoung / Lee, Madeline J / Blish, Catherine A / Deeks, Steven G / Greene, Warner C / Lee, Sulggi A / Roan, Nadia R

Frontiers in immunology

2022 Volume 13, Page(s) 803417

Abstract: T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV ( ... ...

Abstract	T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV (PLWH), particularly from those who initiated antiretroviral therapy (ART) during acute infection. Our study design was to use 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers (N = 5), and ART-suppressed individuals who had started therapy during chronic (N = 6) vs. acute infection (N = 8), the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5- counterparts. In addition, a subset of memory-like CD56
MeSH term(s)	Adult ; Aged ; Anti-Retroviral Agents/therapeutic use ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Killer Cells, Natural/immunology ; Leukocytes/classification ; Leukocytes/immunology ; Lymphocytes/classification ; Lymphocytes/immunology ; Male ; Middle Aged ; Phenotype ; Sustained Virologic Response
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2022-01-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.803417
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Article ; Online: Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8

Ma, Tongcui / Ryu, Heeju / McGregor, Matthew / Babcock, Benjamin / Neidleman, Jason / Xie, Guorui / George, Ashley F / Frouard, Julie / Murray, Victoria / Gill, Gurjot / Ghosn, Eliver / Newell, Evan W / Lee, Sulggi A / Roan, Nadia R

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 207, Issue 5, Page(s) 1344–1356

Abstract: ... ...

Abstract	CD8
MeSH term(s)	CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; COVID-19/immunology ; Convalescence ; Humans ; Longitudinal Studies ; SARS-CoV-2/immunology
Language	English
Publishing date	2021-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100465
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Article ; Online: mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status

Jason Neidleman / Xiaoyu Luo / Matthew McGregor / Guorui Xie / Victoria Murray / Warner C Greene / Sulggi A Lee / Nadia R Roan

eLife, Vol

2021 Volume 10

Abstract	While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.
Keywords	COVID-19 ; SARS-CoV-2 ; mRNA vaccine ; antigen-specific T cells ; CyTOF ; lymphocyte subsets ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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