Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the TFH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary

Leong, Yew Ann; Yu, Di

doi:10.3389/fimmu.2017.00622

Cited by 8 publications

(4 citation statements)

References 161 publications

(229 reference statements)

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“…In particular, PD-L1 hi EBV + HL and DLBCL tumor cells may be suitable therapeutic targets for anti-PD-1/PD-L1 immunotherapy with the aim to unleash host antitumor immune responses. Moreover, the recently identified roles of Tfh cells, FDCs, and FRCs as HIV-1 reservoirs or targets, potentially involved in early and late relapse to ART, could provide new prognosis biomarkers and therapeutic targets, including the use of antifibrotic molecules to revert HIV-1-induced damage to lymphoid stromal cell niches, the purging of the FDC reservoir, or the targeting of infected Tfh cells ( 111 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response

Rodriguez¹,

Roussel²,

Tarte³

et al. 2017

Front. Immunol.

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During the last decades, considerable efforts have been done to decipher mechanisms supported by microorganisms or viruses involved in the development, differentiation, and function of immune cells. Pathogens and their associated secretome as well as the continuous inflammation observed in chronic infection are shaping both innate and adaptive immunity. Secondary lymphoid organs are functional structures ensuring the mounting of adaptive immune response against microorganisms and viruses. Inside these organs, germinal centers (GCs) are the specialized sites where mature B-cell differentiation occurs leading to the release of high-affinity immunoglobulin (Ig)-secreting cells. Different steps are critical to complete B-cell differentiation process, including proliferation, somatic hypermutations in Ig variable genes, affinity-based selection, and class switch recombination. All these steps require intense interactions with cognate CD4+ helper T cells belonging to follicular helper lineage. Interestingly, pathogens can disturb this subtle machinery affecting the classical adaptive immune response. In this review, we describe how viruses could act directly on GC B cells, either through B-cell infection or by their contribution to B-cell cancer development and maintenance. In addition, we depict the indirect impact of viruses on B-cell response through infection of GC T cells and stromal cells, leading to immune response modulation.

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Section: Discussionmentioning

confidence: 99%

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response

Rodriguez¹,

Roussel²,

Tarte³

et al. 2017

Front. Immunol.

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“…TFH cells have been demonstrated to be both productively (i.e., vRNA + ) and latently (i.e., vDNA) infected at higher frequencies ( 5 , 56 ) than non-TFH cells. TFH cells are in the vicinity of cells harboring virus-immune complexes like FDCs and B cells ( 57 – 59 ) that serve as a significant reservoir and are able to effectively infect CD4 + T cells in vitro ( 41 , 60 , 61 ). Their unique localization in combination with their activation status could contribute to the higher infection levels of TFH cells in vivo .…”

Section: Tfh Cells: a Preferential Hiv/siv Reservoirmentioning

confidence: 99%

“…The transcriptional suppressor BCL-6 has been shown to suppress the expression of antiviral genes in TFH cells ( 61 , 72 ). Indeed, several genes are under direct or indirect control of BCL-6 and are positively correlated to the maintenance of HIV reservoir (IntDNA) and to the other viral outcomes (TILDA and VL) (Figure 2 A).…”

Section: Molecular Pathways Promoting Tfh Susceptibility To Hiv Infecmentioning

confidence: 99%

“…Indeed, several genes are under direct or indirect control of BCL-6 and are positively correlated to the maintenance of HIV reservoir (IntDNA) and to the other viral outcomes (TILDA and VL) (Figure 2 A). Conversely, silencing viral gene expression allows the survival of infected cells via two mechanisms: (i) the diminished viral gene expression downregulates viral production, which in turn prevents the virus-induced cytopathic effect and (ii) the reduced antigen presentation on MHC-I prevents recognition by CTLs or natural killer cells and, therefore, prevents cell-mediated cytotoxic killing ( 61 ). The low frequency of HIV-specific CD8 T cells in GC ( 67 ), their impaired cytotoxic capacity compared to their blood counterparts ( 70 ) or even their inability to sense the infected cells could represent cellular mechanisms for this outcome.…”

Section: Molecular Pathways Promoting Tfh Susceptibility To Hiv Infecmentioning

confidence: 99%

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Follicular CD4 T Helper Cells As a Major HIV Reservoir Compartment: A Molecular Perspective

Aïd

Dupuy

Moysi³

et al. 2018

Front. Immunol.

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Effective antiretroviral therapy (ART) has prevented the progression to AIDS and reduced HIV-related morbidities and mortality for the majority of infected individuals. However, a lifelong administration of ART is necessary, placing an inordinate burden on individuals and public health systems. Therefore, discovering therapeutic regimens able to eradicate or functionally cure HIV infection is of great importance. ART interruption leads to viral rebound highlighting the establishment and maintenance of a latent viral reservoir compartment even under long-term treatment. Follicular helper CD4 T cells (TFH) have been reported as a major cell compartment contributing to viral persistence, consequent to their susceptibility to infection and ability to release replication-competent new virions. Here, we discuss the molecular profiles and potential mechanisms that support the role of TFH cells as one of the major HIV reservoirs.

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Glycans with Antiviral Activity from Marine Organisms

Grice

Mariottini

2018

Results and Problems in Cell Differentiation

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There remains today a critical need for new antiviral agents, particularly in view of the alarming increase in drug resistance and associated issues. The marine environment has been a prolific contributor towards the identification of novel therapeutic agents in the recent few decades. Added to this, glycans (or carbohydrate- or sugar-based compounds) have in very recent decades made outstanding contributions to the development of novel therapeutics. This review brings together these significant facets of modern drug discovery by presenting the reported literature on glycans derived from marine organisms that possess antiviral activity.The glycans have been grouped together based on the marine organism they were isolated from, namely, (1) bacteria, (2) chromists, (3) plants and (4) animals. For chromists, glycans are further subsectioned into Ochrophyta (brown algae), Miozoa (according to www.algaebase.org ; also called Myzozoa according to WoRMS, www.marinespecies.org ) (dinoflagellates) and Bacillariophyta (diatoms). For plants, glycans are further subsectioned into Chlorophyta, Rhodophyta and Tracheophyta. Glycans isolated to date are reported as alginates, chitosan, extracellular polysaccharides, fucans (e.g. fucoidans), galactans (e.g. carrageenans), glycolipids, glycosaminoglycans, glycosides, glycosylated haemocyanin, laminarans, mannans, polysaccharides (not defined), rhamnans and xylomannans. Interestingly, many of the glycans displaying antiviral properties are sulfated.Reports indicate that marine-sourced glycans have exhibited antiviral activity against African swine fever virus, cytomegalovirus, dengue virus, Epstein-Barr virus, encephalomyocarditis virus, human immunodeficiency virus, hepatitis C virus, herpes simplex virus, human cytomegalovirus, human papilloma virus, human rhino virus, influenza virus, Japanese encephalitis virus, murine leukaemia virus, murine sarcoma virus, Newcastle disease virus, parainfluenza virus, respiratory syncytial virus, Semliki Forest virus, tobacco mosaic virus, vaccinia virus, varicella zoster virus, viral haemorrhagic septicaemia virus and vesicular stomatitis virus. Selected representative glycan structures are presented in Fig. 20.1.

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Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the TFH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary

Cited by 8 publications

References 161 publications

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response

Impact of Chronic Viral Infection on T-Cell Dependent Humoral Immune Response

Follicular CD4 T Helper Cells As a Major HIV Reservoir Compartment: A Molecular Perspective

Glycans with Antiviral Activity from Marine Organisms

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