Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

Xu, Wei; Li, Haoyang; Wang, Qian; Chen, Hua; Zhang, Hanzhen; Li, Weihua; Jiang, Shibo; Lu, Lu

doi:10.1155/2017/6096134

Cited by 35 publications

(23 citation statements)

References 100 publications

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“…ART has enabled a reduction in HIV transmission, a prolonged life span, and an improved quality of life for PLHIV (45). However, limitations of lifelong adherence to therapy including drug resistance, medication-induced adverse events, and serious non-AIDS events have highlighted the need for a functional cure of infection that aims at achieving long-term drug-free remission in HIV-infected individuals in the absence of an efficacious vaccine or curative strategy (46,47). VNPs are a rare group of HIV-1-infected individuals characterized by non-progression despite intensive viral replication.…”

Section: Discussionmentioning

confidence: 99%

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

et al. 2020

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Viremic non-progressors (VNPs), a distinct group of HIV-1-infected individuals, exhibit no signs of disease progression and maintain persistently elevated CD4+ T cell counts for several years despite high viral replication. Comprehensive characterization of homeostatic cellular immune signatures in VNPs can provide unique insights into mechanisms responsible for coping with viral pathogenesis as well as identifying strategies for immune restoration under clinically relevant settings such as antiretroviral therapy (ART) failure. We report a novel homeostatic signature in VNPs, the preservation of the central memory CD4+ T cell (CD4+ T CM) compartment. In addition, CD4+ T CM preservation was supported by ongoing interleukin-7 (IL-7)-mediated thymic repopulation of naive CD4+ T cells leading to intact CD4+ T cell homeostasis in VNPs. Regulatory T cell (Treg) expansion was found to be a function of preserved CD4+ T cell count and CD4+ T cell activation independent of disease status. However, in light of continual depletion of CD4+ T cell count in progressors but not in VNPs, Tregs appear to be involved in lack of disease progression despite high viremia. In addition to these homeostatic mechanisms resisting CD4+ T cell depletion in VNPs, a relative diminution of terminally differentiated effector subset was observed exclusively in these individuals that might ameliorate consequences of high viral replication. VNPs also shared signatures of impaired CD8+ T cell cytotoxic function with progressors evidenced by increased exhaustion (PD-1 upregulation) and CD127 (IL-7Rα) downregulation contributing to persistent viremia. Thus, the homeostatic immune signatures reported in our study suggest a complex multifactorial mechanism accounting for non-progression in VNPs.

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Section: Discussionmentioning

confidence: 99%

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

et al. 2020

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“…At this juncture, this brings up the question of what type of cure can ultimately be achieved. Sterilizing cure has its drawbacks, such as finding matched donors and potential transplantation complications (Xu et al, 2017). Thus, most of the scientific community believe that a sterilizing cure would not be feasible, and a functional cure is more achievable (Sylla et al, 2018).…”

Section: Hiv Eradication and Cure Research: Barriers And Approachesmentioning

confidence: 99%

Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

Kalidasan

Das

2020

Front. Microbiol.

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There is a continuous search for an HIV cure as the success of ART in blocking HIV replication and the role of CD4 + T cells in HIV pathogenesis and immunity do not entirely eradicate HIV. The Berlin patient, who is virus-free, serves as the best model for a 'sterilizing cure' and many experts are trying to mimic this approach in other patients. Although failures were reported among Boston and Essen patients, the setbacks have provided valuable lessons to strengthen cure strategies. Following the Berlin patient, two more patients known as London and Düsseldorf patients might be the second and third person to be cured of HIV. In all the cases, the patients underwent chemotherapy regimen due to malignancy and hematopoietic stem cell transplantation (HSCT) which required matching donors for CCR5 32 mutation-an approach that may not always be feasible. The emergence of newer technologies, such as long-acting slow-effective release ART (LASER ART) and CRISPR/Cas9 could potentially overcome the barriers due to HIV latency and persistency and eliminate the need for CCR5 32 mutation donor. Appreciating the failure and success stories learned from these HIV breakthroughs would provide some insight for future HIV eradication and cure strategies.

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“…However, TALENs and ZFNs are starting to prove their worth in human gene targeting and editing. The biotech company Sangamo Biosciences (California, United States) has stepped forward its ZFN in in vivo gene editing research into the clinic, and the US Food and Drug Administration (US-FDA) has permitted a HIV program in somatic cells (non inherited cells), which has cured more than 80 HIV-infected patients so far ( Xu et al, 2017 ). Meanwhile, TALENs are recently used in the clinic to engineer immune cells to help fight leukemia in a young girl ( Le, 2015 ).…”

Section: Advanced Gene Editing Toolsmentioning

confidence: 99%

Cell Line Techniques and Gene Editing Tools for Antibody Production: A Review

Dangi

Sinha²,

Dwivedi

et al. 2018

Front. Pharmacol.

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The present day modern formulation practices for drugs are based on newer tools and techniques toward effective utilization. The methods of antibody formulations are to be revolutionized based on techniques of cell engineering and gene editing. In the present review, we have discussed innovations in cell engineering toward production of novel antibodies for therapeutic applications. Moreover, this review deciphers the use of RNAi, ribozyme engineering, CRISPR-Cas-based techniques for better strategies for antibody production. Overall, this review describes the multidisciplinary aspects of the production of therapeutic proteins that has gained more attention due to its increasing demand.

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Advancements in Developing Strategies for Sterilizing and Functional HIV Cures

Cited by 35 publications

References 100 publications

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

Delineation of Homeostatic Immune Signatures Defining Viremic Non-progression in HIV-1 Infection

Lessons Learned From Failures and Success Stories of HIV Breakthroughs: Are We Getting Closer to an HIV Cure?

Cell Line Techniques and Gene Editing Tools for Antibody Production: A Review

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