Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure

Zaongo, Silvere D.; Ma, Ping; Song, Fangzhou; Chen, Yao-Kai

doi:10.1097/cm9.0000000000001797

Cited by 6 publications

(8 citation statements)

References 149 publications

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“…It has been demonstrated that latently infected CD4+ T-cells (untreated) display two cell clusters (Cluster 1 and Cluster 2) (63). That is important, as these 2 distinct clusters remain despite treatment with (i) SAHA, a less efficient latency reversing agent (LRA) as shown in the literature (64) or (ii) TCR stimulation (65), which works as a potent LRA. HIV transcript levels were consistently higher in cluster 2 than in cluster 1.…”

Section: Identification Of the Inducible Latent Cell And Potential La...mentioning

confidence: 91%

“…Before 2018, researchers using single-cell approaches were oriented to the investigation of cellular heterogeneity of the latent reservoir (45,70), and the assessment of cellular response heterogeneity to latency reversal agents (LRAs) (71). This is understandable, as latent reservoirs represent the greatest challenge to HIV eradication (72), and the application of LRAs to reverse latency is one of the strategies that has been explored to treat patients (65). For example, Baxter et al (45), found that latent reservoirs (CD4 + T-cells) from HIV-untreated individuals were predominantly central/transitional memory (Tcm/tm, CD27 + CD45RA -) and Tem (CD27 -CD45RA -) when stimulated with bryostatin [an antineoplastic drug used in clinical cancer trials (73), and also used as an LRA (65)], or not.…”

Section: Characterization Of Hiv-1 Reservoir Diversitymentioning

confidence: 99%

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Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature

2022

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Knowledge gaps remain in the understanding of HIV disease establishment and progression. Scientists continue to strive in their endeavor to elucidate the precise underlying immunopathogenic mechanisms of HIV-related disease, in order to identify possible preventive and therapeutic targets. A useful tool in the quest to reveal some of the enigmas related to HIV infection and disease is the single-cell sequencing (scRNA-seq) technique. With its proven capacity to elucidate critical processes in cell formation and differentiation, to decipher critical hematopoietic pathways, and to understand the regulatory gene networks that predict immune function, scRNA-seq is further considered to be a potentially useful tool to explore HIV immunopathogenesis. In this article, we provide an overview of single-cell sequencing platforms, before delving into research findings gleaned from the use of single cell sequencing in HIV research, as published in recent literature. Finally, we describe two important avenues of research that we believe should be further investigated using the single-cell sequencing technique.

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Section: Identification Of the Inducible Latent Cell And Potential La...mentioning

confidence: 91%

Section: Characterization Of Hiv-1 Reservoir Diversitymentioning

confidence: 99%

Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature

2022

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“…“Shock and Kill” aims to reverse HIV latency and increase viral gene expression [Figure 2 A], followed by clearance of infected cells via immune-mediated killing by NK cells, CTLs and bNAbs. [ 57 ] However, “Shock and Kill” has been challenging to achieve. The localization of reactivated CD4 + T cells in protected sites, insufficient expression of HIV Ags by reactivated CD4 + T cells, low levels and impaired function of HIV-specific CD8 + T cells, and presence of CTL escape mutants might affect the effectiveness of “Shock and Kill” strategies.…”

Section: Immune Interventions For Hiv Curementioning

confidence: 99%

HIV reservoir: antiviral immune responses and immune interventions for curing HIV infection

Moog

Zhang

et al. 2022

Chinese Medical Journal

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Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.

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“…Despite extensive global research and study (1)(2)(3), a cure for HIV infection has, thus far, proven elusive. Recently, our research group has proposed novel potential therapeutic options for HIV infection (4,5) which, we believe, could inspire future clinical trials into curative therapeutic options for HIV. Our first proposition concerns the promotion of P-selectin glycoprotein ligand 1 (PSGL-1), an important receptor from innate immunity, which (i) induces the production of membrane defective virions that are unable to attach to or infect new target cells, and (ii) blocks the HIV reverse transcription process.…”

Section: Introductionmentioning

confidence: 99%

HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection

et al. 2022

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Human immunodeficiency virus (HIV) selectively targets and destroys the infection-fighting CD4+ T-lymphocytes of the human immune system, and has a life cycle that encompasses binding to certain cells, fusion to that cell, reverse transcription of its genome, integration of its genome into the host cell DNA, replication of the HIV genome, assembly of the HIV virion, and budding and subsequent release of free HIV virions. Once a host is infected with HIV, the host’s ability to competently orchestrate effective and efficient immune responses against various microorganisms, such as viral infections, is significantly disrupted. Without modern antiretroviral therapy (ART), HIV is likely to gradually destroy the cellular immune system, and thus the initial HIV infection will inexorably evolve into acquired immunodeficiency syndrome (AIDS). Generally, HIV infection in a patient has an acute phase, a chronic phase, and an AIDS phase. During these three clinical stages, patients are found with relatively specific levels of viral RNA, develop rather distinctive immune conditions, and display unique clinical manifestations. Convergent research evidence has shown that hepatitis B virus (HBV) co-infection, a common cause of chronic liver disease, is fairly common in HIV-infected individuals. HBV invasion of the liver can be facilitated by HIV infection at each clinical stage of the infection due to a number of contributing factors, including having identical transmission routes, immunological suppression, gut microbiota dysbiosis, poor vaccination immune response to hepatitis B immunization, and drug hepatotoxicity. However, there remains a paucity of research investigation which critically describes the influence of the different HIV clinical stages and their consequences which tend to favor HBV entrenchment in the liver. Herein, we review advances in the understanding of the mechanisms favoring HBV infection at each clinical stage of HIV infection, thus paving the way toward development of potential strategies to reduce the prevalence of HBV co-infection in the HIV-infected population.

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Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure

Cited by 6 publications

References 149 publications

Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature

Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature

HIV reservoir: antiviral immune responses and immune interventions for curing HIV infection

HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection

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