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[PMID]:29324751
[Au] Autor:Echebli N; Tchitchek N; Dupuy S; Bruel T; Peireira Bittencourt Passaes C; Bosquet N; Le Grand R; Bourgeois C; Favier B; Cheynier R; Lambotte O; Vaslin B
[Ad] Endereço:CEA, Université Paris Sud, INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department / IBFJ, Fontenay-aux-Roses, France.
[Ti] Título:Stage-specific IFN-induced and IFN gene expression reveal convergence of type I and type II IFN and highlight their role in both acute and chronic stage of pathogenic SIV infection.
[So] Source:PLoS One;13(1):e0190334, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interferons (IFNs) play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon stimulated genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques to understand the respective roles of type I and type II IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection and to some extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression persisted during the chronic phase, in contrast to undetectable induction of type I IFN expression. Global gene expression analysis with a major focus on ISGs revealed that at both acute and chronic infection phases most differentially expressed ISGs were inducible by both type I and type II IFNs and displayed the highest increases, indicating strong convergence and synergy between type I and type II IFNs. The analysis of functional signatures of ISG expression revealed temporal changes in IFN expression patterns identifying phase-specific ISGs. These results suggest that IFN-γ strongly contribute to shape ISG upregulation in addition to type I IFN.
[Mh] Termos MeSH primário: Expressão Gênica
Interferon Tipo I/genética
Interferon gama/genética
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
[Mh] Termos MeSH secundário: Doença Aguda
Animais
Doença Crônica
Macaca fascicularis
Vírus da Imunodeficiência Símia/imunologia
Vírus da Imunodeficiência Símia/fisiologia
Transcriptoma
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Interferon Type I); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190334


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[PMID]:29220358
[Au] Autor:Dorta-Estremera S; Nehete PN; Yang G; He H; Nehete BP; Shelton KA; Barry MA; Sastry KJ
[Ad] Endereço:The University of Texas MD Anderson Cancer Center, Department of Immunology, Houston, TX, United States of America.
[Ti] Título:Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques.
[So] Source:PLoS One;12(12):e0188807, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Studies in nonhuman primates (NHP) for prospective immune cell monitoring subsequent to infection and/or vaccination usually rely on periodic sampling of the blood samples with only occasional collections of biopsies from mucosal tissues because of safety concerns and practical constraints. Here we present evidence in support of cytobrush sampling of oral, rectal, and genital mucosal tissues as a minimally invasive approach for the phenotypic analyses of different T cells subsets de novo as well as prospectively after intranasal immunization in rhesus macaques. Significant percentages of viable lymphocytes were obtained consistently from both naïve and chronically SIV-infected rhesus macaques. The percentages of CD3+ T cells in the blood were significantly higher compared to those in the mucosal tissues analyzed in the naïve animals, while in the SIV+ animals the CD3+ T cells were significantly elevated in the rectal tissues, relative to all other sites analyzed. In the naïve, but not SIV+ macaques, the rectal and vaginal mucosal tissues, compared to oral mucosa and blood, showed higher diversity and percentages of CD4+ T cells expressing the HIV entry co-receptor CCR5 and mucosal specific adhesion (CD103) as well as activation (HLA-DR) and proliferation (Ki67) markers. Sequential daily cytobrush sampling from the oral, rectal, and genital mucosal tissues was performed in SIV+ animals from an ongoing study where they were administered intranasal immunization with adenoviral vectored vaccines incorporating the green fluorescent protein (GFP) reporter gene. We detected a transient increase in GFP+ CD4 T cells in only oral mucosa suggesting limited mucosal trafficking. In general, CD4+ and CD8+ T cells expressing Ki67 transiently increased in all mucosal tissues, but those expressing the CCR5, HLA-DR, and CD103 markers exhibited minor changes. We propose the minimally invasive cytobrush sampling as a practical approach for effective and prospective immune monitoring of the oral-genital mucosal tissues in NHP.
[Mh] Termos MeSH primário: Contagem de Linfócito CD4
Linfócitos T CD4-Positivos/imunologia
Macaca mulatta/imunologia
Membrana Mucosa/imunologia
Vacinas Virais/administração & dosagem
[Mh] Termos MeSH secundário: Administração Intranasal
Animais
Feminino
Citometria de Fluxo
Masculino
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Vacinas Virais/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Vaccines)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180218
[Lr] Data última revisão:
180218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188807


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[PMID]:28463876
[Au] Autor:Anderson DJ; Politch JA; Zeitlin L; Hiatt A; Kadasia K; Mayer KH; Ruprecht RM; Villinger F; Whaley KJ
[Ad] Endereço:aDepartments of Obstetrics and Gynecology Boston University School of Medicine, Boston, Massachusetts bMapp Biopharmaceutical, San Diego California cDepartment of Molecular Medicine, Boston University School of Medicine dFenway Health, Harvard Medical School, Boston, Massachusetts eTexas Biomedical Institute, Southwest National Primate Research Center, San Antonio, Texas fNew Iberia Primate Center, New Iberia, Louisiana, USA.
[Ti] Título:Systemic and topical use of monoclonal antibodies to prevent the sexual transmission of HIV.
[So] Source:AIDS;31(11):1505-1517, 2017 Jul 17.
[Is] ISSN:1473-5571
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:: Passive immunization, the transfer of antibodies to a nonimmune individual to provide immunological protection, has been used for over 100 years to prevent and treat human infectious diseases. The introduction of techniques to produce human mAbs has revolutionized the field, and a large number of human mAbs have been licensed for the treatment of cancer, autoimmune and inflammatory diseases. With the recent discovery and production of highly potent broadly neutralizing and other multifunctional antibodies to HIV, mAbs are now being considered for HIV therapy and prophylaxis. In this review, we briefly present recent advances in the anti-HIV mAb field and outline strategies for the selection, engineering and production of human mAbs, including the modification of their structure for optimized stability and function. We also describe results from nonhuman primate studies and phase 1 clinical trials that have tested the safety, tolerability, pharmacokinetics, and efficacy of mAb-based HIV prevention strategies, and discuss the future of parenteral and topical mAb administration for the prevention of HIV transmission.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Anticorpos Monoclonais/farmacologia
Anticorpos Anti-HIV/efeitos dos fármacos
Anticorpos Anti-HIV/imunologia
Infecções por HIV/prevenção & controle
Imunização Passiva
Profilaxia Pré-Exposição/métodos
Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
[Mh] Termos MeSH secundário: Administração Tópica
Animais
Anticorpos Monoclonais/administração & dosagem
Feminino
Infecções por HIV/transmissão
HIV-1/efeitos dos fármacos
Seres Humanos
Imunização Passiva/métodos
Reto/virologia
Síndrome de Imunodeficiência Adquirida dos Símios/transmissão
Vírus da Imunodeficiência Símia/efeitos dos fármacos
Resultado do Tratamento
Vagina/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (HIV Antibodies)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1097/QAD.0000000000001521


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[PMID]:29229308
[Au] Autor:Mangus LM; Beck SE; Queen SE; Brill SA; Shirk EN; Metcalf Pate KA; Muth DC; Adams RJ; Gama L; Clements JE; Mankowski JL
[Ad] Endereço:Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
[Ti] Título:Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.
[So] Source:Am J Pathol;188(1):125-134, 2018 01.
[Is] ISSN:1525-2191
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20 B cells and CD3 T cells with fewer CD68 macrophages. Inflammation was associated with low levels of SIV RNA in the brain as shown by in situ hybridization, and generally was observed in animals with episodes of cerebrospinal fluid (CSF) viral rebound or sustained plasma and CSF viremia during treatment. Although the lymphocytic CNS inflammation in these macaques shared morphologic characteristics with uncommon immune-mediated neurologic disorders reported in treated HIV patients, including CNS immune reconstitution inflammatory syndrome and neurosymptomatic CSF escape, the high prevalence of CNS lesions in macaques suggests that persistent adaptive immune responses in the CNS also may develop in neuroasymptomatic or mildly impaired HIV patients yet remain unrecognized given the lack of access to CNS tissue for histopathologic evaluation. Continued investigation into the mechanisms and outcomes of CNS inflammation in cART-treated, SIV-infected macaques will advance our understanding of the consequences of residual CNS HIV replication in patients on cART, including the possible contribution of adaptive immune responses to HIV-associated neurocognitive disorders.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Encéfalo/patologia
Encefalite/patologia
Linfócitos/patologia
Meningite/patologia
Síndrome de Imunodeficiência Adquirida dos Símios/patologia
[Mh] Termos MeSH secundário: Animais
Encefalite/complicações
Inflamação/patologia
Macaca nemestrina
Masculino
Meningite/complicações
Síndrome de Imunodeficiência Adquirida dos Símios/complicações
Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico
Vírus da Imunodeficiência Símia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Anti-Retroviral Agents)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


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[PMID]:28465428
[Au] Autor:Jiang G; Santos Rocha C; Hirao LA; Mendes EA; Tang Y; Thompson GR; Wong JK; Dandekar S
[Ad] Endereço:Department of Medical Microbiology and Immunology, University of California, Davis, California, USA.
[Ti] Título:HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection.
[So] Source:MBio;8(3), 2017 May 02.
[Is] ISSN:2150-7511
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4 T cell cultures and a simian immunodeficiency virus (SIV) model of AIDS Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4 T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV as well as in the primary CD4 T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy. Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and treatment strategies. Most investigations focused on the viral pathogenic mechanisms leading to immune dysfunction following robust viral infection and dissemination. Less is known about mechanisms that enable HIV to establish its presence despite rapid onset of host antiviral innate response. Our novel findings provide insights into the viral strategy that hijacks the host innate response of the suppression of protein biosynthesis to restrict the virus production. The virus leverages transcription factor ATF4 expression during the GCN2-ATF4 signaling response and utilizes it to activate viral transcription through the LTR to support viral transcription and production in both HIV and SIV infections. This unique viral strategy is exploiting the innate response and is distinct from the mechanisms of immune dysfunction after the critical mass of viral loads is generated.
[Mh] Termos MeSH primário: Fator 4 Ativador da Transcrição/metabolismo
Linfócitos T CD4-Positivos/virologia
HIV-1/fisiologia
Interações Hospedeiro-Patógeno
Imunidade Inata
Proteínas Serina-Treonina Quinases/metabolismo
Replicação Viral
[Mh] Termos MeSH secundário: Fator 4 Ativador da Transcrição/genética
Animais
Linfócitos T CD4-Positivos/efeitos dos fármacos
Células Cultivadas
Modelos Animais de Doenças
Trato Gastrointestinal/virologia
Infecções por HIV/tratamento farmacológico
Infecções por HIV/imunologia
Infecções por HIV/virologia
HIV-1/imunologia
HIV-1/patogenicidade
Seres Humanos
Evasão da Resposta Imune
Macaca mulatta
Proteínas Serina-Treonina Quinases/genética
Selênio/farmacologia
Transdução de Sinais
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/virologia
Vírus da Imunodeficiência Símia
Carga Viral
Latência Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATF4 protein, human); 145891-90-3 (Activating Transcription Factor 4); EC 2.7.11.1 (EIF2AK4 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); H6241UJ22B (Selenium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:29267382
[Au] Autor:Zhang Z; Gu Q; de Manuel Montero M; Bravo IG; Marques-Bonet T; Häussinger D; Münk C
[Ad] Endereço:Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
[Ti] Título:Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans.
[So] Source:PLoS Pathog;13(12):e1006746, 2017 12.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:APOBEC3s (A3s) are potent restriction factors of human immunodeficiency virus type 1/simian immunodeficiency viruses (HIV-1/SIV), and can repress cross-species transmissions of lentiviruses. HIV-1 originated from a zoonotic infection of SIV of chimpanzee (SIVcpz) to humans. However, the impact of human A3s on the replication of SIVcpz remains unclear. By using novel SIVcpz reporter viruses, we identified that human APOBEC3B (A3B) and APOBEC3H (A3H) haplotype II strongly reduced the infectivity of SIVcpz, because both of them are resistant to SIVcpz Vifs. We further demonstrated that human A3H inhibited SIVcpz by deaminase dependent as well independent mechanisms. In addition, other stably expressed human A3H haplotypes and splice variants showed strong antiviral activity against SIVcpz. Moreover, most SIV and HIV lineage Vif proteins could degrade chimpanzee A3H, but no Vifs from SIVcpz and SIV of gorilla (SIVgor) lineages antagonized human A3H haplotype II. Expression of human A3H hapII in human T cells efficiently blocked the spreading replication of SIVcpz. The spreading replication of SIVcpz was also restricted by stable A3H in human PBMCs. Thus, we speculate that stably expressed human A3H protects humans against the cross-species transmission of SIVcpz and that SIVcpz spillover to humans may have started in individuals that harbor haplotypes of unstable A3H proteins.
[Mh] Termos MeSH primário: Aminoidrolases/metabolismo
Transmissão de Doença Infecciosa
Síndrome de Imunodeficiência Adquirida dos Símios/transmissão
Vírus da Imunodeficiência Símia
Zoonoses
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Pan troglodytes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.5.4.- (APOBEC3H protein, human); EC 3.5.4.- (Aminohydrolases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180111
[Lr] Data última revisão:
180111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006746


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[PMID]:29261677
[Au] Autor:Steele AK; Carrasco-Medina L; Sodora DL; Crawley AM
[Ad] Endereço:Center for Infectious Disease Research, Seattle, WA, United States of America.
[Ti] Título:Increased soluble IL-7 receptor concentrations associate with improved IL-7 therapy outcomes in SIV-infected ART-treated Rhesus macaques.
[So] Source:PLoS One;12(12):e0188427, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. This study furthers our knowledge regarding the interrelationship between increased IL-7 levels and elevated sCD127 levels that may have implications for future IL-7 immunotherapeutic approaches in HIV-infected patients.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Interleucina-7/uso terapêutico
Receptores de Interleucina-7/metabolismo
Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico
Síndrome de Imunodeficiência Adquirida dos Símios/virologia
Vírus da Imunodeficiência Símia/fisiologia
[Mh] Termos MeSH secundário: Animais
Antirretrovirais/farmacologia
Linfócitos T CD8-Positivos/imunologia
Sobrevivência Celular/imunologia
Interleucina-7/administração & dosagem
Interleucina-7/farmacologia
Ativação Linfocitária/imunologia
Contagem de Linfócitos
Macaca mulatta
Receptores de Interleucina-7/sangue
Síndrome de Imunodeficiência Adquirida dos Símios/sangue
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Vírus da Imunodeficiência Símia/efeitos dos fármacos
Solubilidade
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (Interleukin-7); 0 (Receptors, Interleukin-7); 0 (interleukin-7 receptor, alpha chain)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188427


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[PMID]:27779180
[Au] Autor:Kotb A; Klippert A; Daskalaki M; Sauermann U; Stahl-Hennig C; Neumann B
[Ad] Endereço:Unit of Infection Models, German Primate Center, Leibniz Institute for Primate Research, Goettingen, Germany.
[Ti] Título:Elevated granzyme B B-cell level in SIV-infection correlate with viral load and low CD4 T-cell count.
[So] Source:Immunol Cell Biol;95(3):316-320, 2017 03.
[Is] ISSN:1440-1711
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Granzyme B-expressing (GrB ) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts. When investigating GrB B cells in different compartments, levels were highest in blood, spleen and bone marrow, but considerably lower in lymph nodes and tonsils. Analysis of expression of various surface markers on this particular B-cell subset in SIV-infected macaques revealed differences between the phenotype in macaques and in humans. GrB B cells in SIV-infected rhesus macaques exhibit an elevated expression of CD5, CD10, CD25 and CD27, while expression of CD19, CD185 and HLA-DR is reduced. In contrast to human GrB B cells, we did not observe a significantly increased expression of CD43 and CD86. B-cell receptor stimulation in combination with IL-21 of purified B cells from healthy animals led to the induction of GrB expression. Furthermore, initial functional analyses indicated a regulatory role on T-cell proliferation. Overall, our data pave the way for longitudinal analyses including studies on the functionality of GrB B cells in the nonhuman primate model for AIDS.
[Mh] Termos MeSH primário: Linfócitos B/metabolismo
Linfócitos T CD4-Positivos/imunologia
Granzimas/metabolismo
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/virologia
Vírus da Imunodeficiência Símia/fisiologia
Carga Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Contagem de Linfócito CD4
Progressão da Doença
Feminino
Seres Humanos
Interleucina-10/metabolismo
Macaca mulatta
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
130068-27-8 (Interleukin-10); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171216
[Lr] Data última revisão:
171216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1038/icb.2016.96


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[PMID]:29073258
[Au] Autor:Bailey AL; Buechler CR; Matson DR; Peterson EJ; Brunner KG; Mohns MS; Breitbach M; Stewart LM; Ericsen AJ; Newman CM; Koenig MR; Mohr E; Tan J; Capuano S; Simmons HA; Yang DT; O'Connor DH
[Ad] Endereço:Wisconsin National Primate Research Center, Madison, Wisconsin, United States of America.
[Ti] Título:Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection.
[So] Source:PLoS Pathog;13(10):e1006692, 2017 Oct.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the mechanism of this protective effect remains poorly understood. We sequentially infected cynomolgus macaques with simian pegivirus (SPgV) and simian immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect on acute-phase SIV pathogenesis-as measured by SIV viral load, CD4+ T cell destruction, immune activation, or adaptive immune responses-suggesting that HPgV's protective effect is exerted primarily during the chronic phase of HIV infection. We also examined the immune response to SPgV in unprecedented detail, and found that this virus elicits virtually no activation of the immune system despite persistently high titers in the blood over long periods of time. Overall, this study expands our understanding of the pegiviruses-an understudied group of viruses with a high prevalence in the global human population-and suggests that the protective effect observed in HIV+HPgV co-infected people occurs primarily during the chronic phase of HIV infection.
[Mh] Termos MeSH primário: Coinfecção/virologia
Infecções por Flaviviridae/imunologia
Infecções por Flaviviridae/virologia
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/virologia
[Mh] Termos MeSH secundário: Animais
Coinfecção/imunologia
Modelos Animais de Doenças
Vírus GB C
Macaca fascicularis
Vírus da Imunodeficiência Símia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006692


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[PMID]:29045906
[Au] Autor:McGary CS; Deleage C; Harper J; Micci L; Ribeiro SP; Paganini S; Kuri-Cervantes L; Benne C; Ryan ES; Balderas R; Jean S; Easley K; Marconi V; Silvestri G; Estes JD; Sekaly RP; Paiardini M
[Ad] Endereço:Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
[Ti] Título:CTLA-4 PD-1 Memory CD4 T Cells Critically Contribute to Viral Persistence in Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.
[So] Source:Immunity;47(4):776-788.e5, 2017 Oct 17.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1 follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4 PD-1 memory CD4 T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus. In contrast to PD-1 Tfh cells, SIV-enriched CTLA-4 PD-1 CD4 T cells were found outside the B cell follicle of the LN, predicted the size of the persistent viral reservoir during ART, and significantly increased their contribution to the SIV reservoir with prolonged ART-mediated viral suppression. We have shown that CTLA-4 PD-1 memory CD4 T cells are a previously unrecognized component of the SIV and HIV reservoir that should be therapeutically targeted for a functional HIV-1 cure.
[Mh] Termos MeSH primário: Antirretrovirais/uso terapêutico
Linfócitos T CD4-Positivos/efeitos dos fármacos
Antígeno CTLA-4/imunologia
Receptor de Morte Celular Programada 1/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico
Vírus da Imunodeficiência Símia/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD4-Positivos/virologia
Antígeno CTLA-4/metabolismo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/imunologia
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
HIV-1/imunologia
HIV-1/fisiologia
Interações Hospedeiro-Patógeno/efeitos dos fármacos
Interações Hospedeiro-Patógeno/imunologia
Seres Humanos
Memória Imunológica/efeitos dos fármacos
Memória Imunológica/imunologia
Hibridização In Situ
Linfonodos/efeitos dos fármacos
Linfonodos/imunologia
Linfonodos/virologia
Macaca mulatta
Microscopia Confocal
Receptor de Morte Celular Programada 1/metabolismo
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/virologia
Vírus da Imunodeficiência Símia/imunologia
Vírus da Imunodeficiência Símia/fisiologia
Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
Linfócitos T Auxiliares-Indutores/imunologia
Linfócitos T Auxiliares-Indutores/virologia
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Retroviral Agents); 0 (CTLA-4 Antigen); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE



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