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Revising the Role of Myeloid cells in HIV Pathogenesis
Anupriya Aggarwal1, Samantha McAllery, Stuart G Turville
1Laboratory of HIV Biology, Immunovirology and Pathogenesis Program, The Kirby Institute, University of New South Wales, Kensington, NSW, 2010, Australia.
Insights
Lentiviruses like HIV can infect resting myeloid cells, including macrophages and dendritic cells (DCs). Despite challenges, these cells are crucial
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Lentiviruses, including HIV, infect resting cells like CD4 T cells, macrophages, and dendritic cells (DCs).
- Myeloid cells (monocytes, macrophages, DCs) are vital for HIV transmission, spread, and serve as viral reservoirs.
- The discovery of the HIV restriction factor SAMHD1 in myeloid cells prompts re-evaluation of their role in HIV pathogenesis.
Purpose of the Study:
- To summarize the role of myeloid cells in HIV pathogenesis.
- To discuss how recent findings reshape the understanding of myeloid cells in HIV infection.
- To highlight myeloid cells as high-value, low-frequency targets for lentiviral infection.
Main Methods:
- Literature review and synthesis of current research on myeloid cells and HIV.
- Analysis of the impact of HIV restriction factors, such as SAMHD1, on myeloid cell permissiveness.
- Conceptual framework development on myeloid cells as 'quality' rather than 'quantity' HIV substrates.
Main Results:
- Myeloid cells, despite potential restriction factors, remain significant targets for lentiviral infection.
- Infection of resting myeloid cells, though infrequent, offers distinct advantages for viral propagation.
- Recent discoveries have nuanced, but not entirely overturned, the established view of myeloid cells in HIV pathogenesis.
Conclusions:
- Myeloid cells are critical, albeit challenging, targets for lentiviruses like HIV.
- The 'quality over quantity' model emphasizes the strategic importance of infecting these specific cell types.
- Understanding lentiviral interaction with myeloid cells is key to developing effective HIV therapies and interventions.
Abstract:
Lentiviruses are characterized by their ability to infect resting cells, such as CD4 T cells, macrophages and dendritic cells (DC). Cells of myeloid lineage, which herein we include including monocytes, macrophages, and dendritic cells, play a pivotal role in HIV infection by not only promoting transmission and spread but also serving as viral reservoirs. However, the recent discovery of the HIV restriction factor SAMHD1 within myeloid cells has again led us to question the role of this lineage both in HIV transmission and pathogenesis. Herein we will summarize what the potential role of myeloid cells in HIV pathogenesis is and how recent observations have or haven't reshaped this view. Finally we highlight the idea that cells of myeloid lineage are quality rather than quantity HIV substrates. Thus, whilst is may indeed be difficult for a lentivirus like HIV to infect a resting cell like a macrophage and/or Dendritic cell, there are significant benefits in doing so, even at low frequency.
