Immunological approaches to HIV cure

Ward, Adam R.; Mota, Talia M.; Jones, R. Brad

doi:10.1016/j.smim.2020.101412

Cited by 52 publications

(44 citation statements)

References 341 publications

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“…Current antiretroviral therapy recommended for HIV-infected subjects requires daily and indefinitely medication that is stressful and not without side effects, especially for younger patients. Moreover, the life-long need for therapy adherence implies high costs of chronic treatment and encourage the exploration of alternative approaches such as immunotherapy that could potentially be complementary to long-term management of HIV infection ( Palma et al, 2013 ; Ward et al, 2020 ). To conclude, plant small RNAs from Moringa oleifera may restore normalcy in immune system and reduce replication of HIV-infection, also at the level of cellular reservoir.…”

Section: Discussionmentioning

confidence: 99%

Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection

et al. 2021

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Traditional medicine is often chosen due to its affordability, its familiarity with patient’s cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-kingdom manner. The aim of the study was to evaluate the effects of plant-enriched purified extract microRNAs from Moringa oleifera seeds (MO) on the immune response and on HIV infection. Bioinformatic analysis shows that plant microRNAs (p-miRs) from MO belonging to 18 conserved families, including p-miR160h, p-miR166, p-miR482b, p-miR159c, p-miR395d, p-miR2118a, p-miR393a, p-miR167f-3p, and p-miR858b are predicted to target with high affinity BCL2, IL2RA, TNF, and VAV1, all these being involved in the cell cycle, apoptosis, immune response and also in the regulation of HIV pathogenesis. The effects of MO p-miRs transfected into HIV+ PBMCs were analyzed and revealed a decrease in viability associated with an increase of apoptosis; an increase of T helper cells expressing Fas and a decrease of intracellular Bcl2 protein expression. Meanwhile no effects were detected in PBMCs from healthy donors. In CD4+ T cells, transfection significantly reduced cell activation and modified the T cell differentiation, thereby decreasing both central and effector memory cells while increasing terminal effector memory cells. Interestingly, the p-miRs transfection induces a reduction of intracellular HIV p24 protein and a reduction of viral DNA integration. Finally, we evaluated the effect of synthetic (mimic) p-miR858b whose sequence is present in the MO p-miR pool and predicted to target VAV1, a protein involved in HIV-Nef binding. This protein plays a pivotal role in T cell antigen receptor (TCR) signaling, so triggering the activation of various pathways. The transfection of HIV+ PBMCs with the synthetic p-miR858b showed a reduced expression of VAV1 and HIV p24 proteins. Overall, our evidence defines putative mechanisms underlying a supplementary benefit of traditional medicine, alongside current antiretroviral therapy, in managing HIV infection in resource-limited settings where MO remains widely available.

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Section: Discussionmentioning

confidence: 99%

Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection

et al. 2021

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“…Ongoing and Emerging Biomedical Research : HIV cure research involves a variety of biomedical approaches, including cell and gene therapies [ 38 ], stem cell transplants [ 39 ], immune-based strategies [ 40 , 41 ], early and intensified HIV therapy [ 42 ], and latency-reversing agents [ 43 , 44 ] among others. These strategies can also be used in combination.…”

Section: Discussionmentioning

confidence: 99%

Ethics of HIV cure research: an unfinished agenda

et al. 2021

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Background The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. Methods We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. Discussion Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). Conclusion HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.

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“…The advent of ART has enabled people living with HIV to confront this situation as a chronic illness more than a fatal disease. However, HIV is not completely eradicated by ART and it persists in specific cells or tissues that act as reservoirs where viral replication continues under different conditions [ 201 , 202 ]. HIV can access the CNS, in part through the transmigration of infected peripheral monocytes that differentiate into macrophages and that can infect other brain resident cells.…”

Section: How Psychostimulants Can Influence Hiv Infectionmentioning

confidence: 99%

“…To better characterize the immune mechanisms affected by psychostimulants in association with HIV progression, it would be helpful to consider the tools the immune system uses effectively against HIV. This information can be partially obtained from the exceptional cases of “elite controllers” and “post-treatment controllers”, individuals who control infection (analogous to functional cures) without or after ART treatment, respectively [ 202 , 206 , 207 ]. Distinct and varied mechanisms are involved in both cases, with a sustained and highly potent HIV-specific CD8 + T-cell and natural killer (NK) response in elite controllers [ 208 , 209 ], and a weaker activation of T-cells, particularly CD4 + cells, in post-treatment controllers [ 207 ].…”

Section: How Psychostimulants Can Influence Hiv Infectionmentioning

confidence: 99%

A “Drug-Dependent” Immune System Can Compromise Protection against Infection: The Relationships between Psychostimulants and HIV

Assis

Carranza

Ambrosio

2021

Viruses

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Psychostimulant use is a major comorbidity in people living with HIV, which was initially explained by them adopting risky behaviors that facilitate HIV transmission. However, the effects of drug use on the immune system might also influence this phenomenon. Psychostimulants act on peripheral immune cells even before they reach the central nervous system (CNS) and their effects on immunity are likely to influence HIV infection. Beyond their canonical activities, classic neurotransmitters and neuromodulators are expressed by peripheral immune cells (e.g., dopamine and enkephalins), which display immunomodulatory properties and could be influenced by psychostimulants. Immune receptors, like Toll-like receptors (TLRs) on microglia, are modulated by cocaine and amphetamine exposure. Since peripheral immunocytes also express TLRs, they may be similarly affected by psychostimulants. In this review, we will summarize how psychostimulants are currently thought to influence peripheral immunity, mainly focusing on catecholamines, enkephalins and TLR4, and shed light on how these drugs might affect HIV infection. We will try to shift from the classic CNS perspective and adopt a more holistic view, addressing the potential impact of psychostimulants on the peripheral immune system and how their systemic effects could influence HIV infection.

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Immunological approaches to HIV cure

Cited by 52 publications

References 341 publications

Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection

Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection

Ethics of HIV cure research: an unfinished agenda

A “Drug-Dependent” Immune System Can Compromise Protection against Infection: The Relationships between Psychostimulants and HIV

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