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Targeting CCR5: A central approach to HIV treatment and cure strategies
Yunus Yukselten1, Hanan Wishah1, Jessica A Li1
1Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, United States.
Abstract:
CCR5, a co-receptor critical for R5-tropic HIV entry into host cells, remains a key target for therapeutic interventions. HIV utilizes CCR5, expressed on T cells and macrophages, to facilitate viral entry. Genetic variants, such as the CCR5Δ32 homozygous mutation that confers protection to HIV infection, have made CCR5 a main target for gene-editing technologies, small-molecule inhibitors, and monoclonal antibody-based therapies. Recent studies emphasize the importance of regulating CCR5 expression at transcriptional and post-transcriptional levels and integrating this approach with traditional therapies. Particularly, the role of heterozygous CCR5Δ32 carriers who are HIV seropositive highlights the potential for targeting CCR5 in combination with other immune-regulatory mechanisms. This may lead to more effective treatment strategies and, ultimately, a functional cure for HIV. This minireview discusses the role of CCR5 in HIV pathogenesis and explores the potential of genetic and therapeutic interventions targeting CCR5 as an innovative strategy in the continued battle against HIV.
Insights
Targeting the CCR5 co-receptor is crucial for blocking HIV entry. Genetic modifications and novel therapies targeting CCR5 offer promising strategies for effective HIV treatment and a potential functional cure.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- CCR5 is a key co-receptor for R5-tropic HIV entry into host cells like T cells and macrophages.
- Genetic variants, notably the CCR5Δ32 mutation, influence HIV susceptibility and are targets for therapeutic strategies.
- Understanding CCR5's role is vital for developing effective HIV interventions.
Purpose of the Study:
- To review the role of CCR5 in HIV pathogenesis.
- To explore genetic and therapeutic interventions targeting CCR5 for HIV treatment.
- To discuss novel strategies for a functional HIV cure.
Main Methods:
- Literature review of studies on CCR5 and HIV.
- Analysis of genetic variants and their impact on HIV infection.
- Exploration of therapeutic approaches including gene editing, small molecules, and antibodies.
Main Results:
- CCR5 is essential for HIV entry and a significant therapeutic target.
- The CCR5Δ32 mutation confers protection, highlighting the potential of genetic interventions.
- Combining CCR5 targeting with immune-regulatory mechanisms shows promise for enhanced treatment.
Conclusions:
- Targeting CCR5, through genetic or therapeutic means, is a key strategy in combating HIV.
- Regulating CCR5 expression and leveraging its genetic variants can lead to innovative treatment approaches.
- Combination therapies involving CCR5 modulation may pave the way for a functional cure for HIV.
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