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Start Over Author "VRC, NIAID, NIH" Topic hiv infections
3 results on '"VRC, NIAID, NIH"'

1. Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections.

Author

Anderson EM, Simonetti FR, Gorelick RJ, Hill S, Gouzoulis MA, Bell J, Rehm C, Pérez L, Boritz E, Wu X, Wells D, Hughes SH, Rao V, Coffin JM, Kearney MF, and Maldarelli F

Subjects
Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes virology, Cell Cycle Proteins genetics, DNA, Viral blood, DNA, Viral genetics, Defective Viruses genetics, Genes, gag, HIV Long Terminal Repeat, HIV-1 drug effects, Humans, Immunologic Memory, Multiplex Polymerase Chain Reaction, Proviruses genetics, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets virology, Time Factors, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, HIV-1 genetics, HIV-1 isolation & purification, Leukocytes, Mononuclear virology, Proviruses isolation & purification
Abstract

Combination antiretroviral therapy (cART) controls but does not eradicate HIV infection; HIV persistence is the principal obstacle to curing infections. The proportion of defective proviruses increases during cART, but the dynamics of this process are not well understood, and a quantitative analysis of how the proviral landscape is reshaped after cART is initiated is critical to understanding how HIV persists. Here, we studied longitudinal samples from HIV infected individuals undergoing long term cART using multiplexed Droplet Digital PCR (ddPCR) approaches to quantify the proportion of deleted proviruses in lymphocytes. In most individuals undergoing cART, HIV proviruses that contain gag are lost more quickly than those that lack gag . Increases in the fraction of gag -deleted proviruses occurred only after 1-2 years of therapy, suggesting that the immune system, and/or toxicity of viral re-activation helps to gradually shape the proviral landscape. After 10-15 years on therapy, there were as many as 3.5-5 times more proviruses in which gag was deleted or highly defective than those containing intact gag . We developed a provirus-specific ddPCR approach to quantify individual clones. Investigation of a clone of cells containing a deleted HIV provirus integrated in the HORMAD2 gene revealed that the cells underwent a massive expansion shortly after cART was initiated until the clone, which was primarily in effector memory cells, dominated the population of proviruses for over 6 years. The expansion of this HIV-infected clone had substantial effects on the overall proviral population., Competing Interests: The authors declare no conflict of interest.

Published
2020
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2. Altered immune cell follicular dynamics in HIV infection following influenza vaccination.

Author

Moysi E, Pallikkuth S, De Armas LR, Gonzalez LE, Ambrozak D, George V, Huddleston D, Pahwa R, Koup RA, Petrovas C, and Pahwa S

Subjects
Adult, Antiretroviral Therapy, Highly Active, B-Lymphocytes immunology, B-Lymphocytes pathology, Case-Control Studies, Female, HIV Infections drug therapy, HIV Infections pathology, Humans, Lymph Nodes pathology, Lymphocyte Count, Male, Middle Aged, T-Lymphocytes, Helper-Inducer classification, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer pathology, Vaccination, HIV Infections immunology, Influenza Vaccines immunology, Lymph Nodes immunology
Abstract

HIV infection changes the lymph node (LN) tissue architecture, potentially impairing the immunologic response to antigenic challenge. The tissue-resident immune cell dynamics in virologically suppressed HIV+ patients on combination antiretroviral therapy (cART) are not clear. We obtained LN biopsies before and 10 to 14 days after trivalent seasonal influenza immunization from healthy controls (HCs) and HIV+ volunteers on cART to investigate CD4+ T follicular helper (Tfh) and B cell dynamics by flow cytometry and quantitative imaging analysis. Prior to vaccination, compared with those in HCs, HIV+ LNs exhibited an altered follicular architecture, but harbored higher numbers of Tfh cells and increased IgG+ follicular memory B cells. Moreover, Tfh cell numbers were dependent upon preservation of the follicular dendritic cell (FDC) network and were predictive of the magnitude of the vaccine-induced IgG responses. Interestingly, postvaccination LN samples in HIV+ participants had significantly (P = 0.0179) reduced Tfh cell numbers compared with prevaccination samples, without evidence for peripheral Tfh (pTfh) cell reduction. We conclude that influenza vaccination alters the cellularity of draining LNs of HIV+ persons in conjunction with development of antigen-specific humoral responses. The underlying mechanism of Tfh cell decline warrants further investigation, as it could bear implications for the rational design of HIV vaccines.

Published
2018
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3. Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies

Author

Manuel Leal, Amarendra Pegu, Michael Y. Gerner, Ilias Vagios, Sarah Andrews, Ezequiel Ruiz-Mateos, Eli Boritz, Constantinos Petrovas, Jason Hataye, Luz A. González-Hernández, Ronald N. Germain, Daniel C. Douek, Michael R. Betts, Arik Cooper, Amaranta Rivero, John R. Mascola, Perla M. Del Rio Estrada, Giuseppe Pantaleo, Yuria Ablanedo-Terrazas, David R. Ambrozak, Gustavo Reyes-Terán, Sara Ferrando-Martinez, Fernando Docobo, Joseph P. Casazza, Richard A. Koup, Kristin L. Boswell, Susan Moir, Eirini Moysi, Robert Paris, Claire Deleage, Adrian B. McDermott, Jacob D. Estes, [Petrovas, Constantinos] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Ferrando-Martinez, Sara] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Casazza, Joseph P.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Hataye, Jason] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Ambrozak, David] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Moysi, Eirini] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Boswell, Kristin L.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA, [Gerner, Michael Y.] NIAID, Lab Syst Biol, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Germain, Ronald N.] NIAID, Lab Syst Biol, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Pegu, Amarendra] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Cooper, Arik] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Mascola, John R.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Deleage, Claire] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, BG 535,POB B, Frederick, MD 21702 USA, [Estes, Jacob D.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, BG 535,POB B, Frederick, MD 21702 USA, [Andrews, Sarah] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [McDermott, Adrian B.] NIAID, Immunol Core Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Del Rio Estrada, Perla M.] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Ablanedo-Terrazas, Yuria] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Rivero, Amaranta] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Alicia Gonzalez-Hernandez, Luz] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Reyes-Teran, Gustavo] Inst Nacl Enfermedades Resp, Dept Invest Enfermedades Infecciosas, Mexico City, DF, Mexico, [Boritz, Eli] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA, [Paris, Robert] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA, [Ruiz-Mateos, Ezequiel] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Leal, Manuel] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Docobo, Fernando] Univ Seville, Lab Immunovirol, Hosp Univ Virgen Rocio, Inst Biomed Sevilla,CSIC, Seville 41013, Spain, [Vagios, Ilias] Venizeleio Hosp, Dept Histopathol, Iraklion, Crete, Greece, [Moir, Susan] NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA, [Pantaleo, Giuseppe] Univ Lausanne, Univ Lausanne Hosp, Dept Med, Serv Immunol & Allergy,Serv Infect Dis, CH-1011 Lausanne, Switzerland, [Pantaleo, Giuseppe] Univ Lausanne, Univ Lausanne Hosp, Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland, [Betts, Michael R.] Univ Penn, Dept Microbiol, Ctr AIDS Res, Perelman Sch Med, Philadelphia, PA 19104 USA, [Betts, Michael R.] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA, [Gerner, Michael Y.] Univ Washington, Dept Immunol, Seattle, WA 98109 USA, VRC, NIAID, NIH, Bill and Melinda Gates Foundation, National Cancer Institute, NIH, Redes Telematicas de Investigacion Cooperativa en Salud (RETICS, Red de SIDA), Fondo de Investigacion Sanitaria, and NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Subjects
0301 basic medicine, Expansion, Adult, Male, Palatine Tonsil, Replication, Activation, HIV Infections, Biology, CD8-Positive T-Lymphocytes, HIV Antibodies, Article, Granzymes, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, NK-92, Antibodies, Bispecific, medicine, Cytotoxic T cell, Responses, Humans, Lymphocytes, Antigen-presenting cell, B cell, Lymph-nodes, Aged, Tissue, Perforin, Germinal center, virus diseases, General Medicine, Middle Aged, Natural killer T cell, Virology, Human-immunodeficiency-virus, 030104 developmental biology, medicine.anatomical_structure, Phenotype, 030220 oncology & carcinogenesis, Immunology, Interleukin 12, Effector, Rna, Cytokines, Female, Lymph Nodes
Abstract

Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals. This profile was associated with persistent local immune activation but did not appear to be directly related to local viral replication. Follicular CD8 (fCD8) T cells, despite compromised cytokine polyfunctionality, showed good cytolytic potential characterized by high ex vivo expression of granzyme B and perforin. We used an anti-HIV/anti-CD3 bispecific antibody in a redirected killing assay and found that fCD8 T cells had better killing activity than did non-fCD8 T cells. Our results indicate that CD8 T cells with potent cytolytic activity are recruited to GCs during HIV infection and, if appropriately redirected to kill HIV-infected cells, could be an effective component of an HIV cure strategy.

Published
2017

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