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Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence
Edana Cassol1, Massimo Alfano, Priscilla Biswas
1AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Italy.
Abstract:
HIV infection of mononuclear phagocytes (MP), mostly as tissue macrophages, is a dominant feature in the pathogenesis of HIV disease and its progression to AIDS. Although the general mechanism of infection is not dissimilar to that of CD4+ T lymphocytes occurring via interaction of the viral envelope with CD4 and a chemokine receptor (usually CCR5), other features are peculiar to MP infection. Among others, the long-term persistence of productive infection, sustained by the absence of substantial cell death, and the capacity of the virions to bud and accumulate in intracellular multivesicular bodies (MVB), has conferred to MP the role of "Trojan horses" perpetuating the chronic state of infection. Because the investigation of tissue macrophages is often very difficult for both ethical and practical reasons of accessibility, most studies of in vitro infection rely upon monocyte-derived macrophages (MDM), a methodology hampered by inter-patient variability and lack of uniformity of experimental protocols. A number of cell lines, mostly Mono Mac, THP-1, U937, HL-60, and their derivative chronically infected counterparts (such as U1 and OM-10.1 cell lines) have complemented the MDM system of infection providing useful information on the features of HIV replication in MP. This article describes and compares the most salient features of these different cellular models of MP infection by HIV.
Insights
Human immunodeficiency virus (HIV) infects mononuclear phagocytes (MP), acting as "Trojan horses" that perpetuate chronic infection. This study compares cellular models for studying HIV replication in MP.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Mononuclear phagocytes (MP), primarily tissue macrophages, are central to human immunodeficiency virus (HIV) pathogenesis and Acquired Immunodeficiency Syndrome (AIDS) progression.
- HIV infects MP similarly to CD4+ T lymphocytes but exhibits unique characteristics, including long-term persistent infection without significant cell death and virion accumulation in multivesicular bodies (MVBs).
- MP serve as crucial reservoirs for HIV, contributing to the chronic nature of the infection and disease progression.
Purpose of the Study:
- To describe and compare the key features of various cellular models used for studying HIV infection in mononuclear phagocytes (MP).
- To evaluate the utility of monocyte-derived macrophages (MDM) and established cell lines in understanding HIV replication within MP.
- To highlight the challenges and advantages associated with different in vitro models for MP infection research.
Main Methods:
- Utilizing monocyte-derived macrophages (MDM) as a primary in vitro model for HIV infection studies.
- Employing established cell lines, including Mono Mac, THP-1, U937, HL-60, and their chronically infected derivatives (U1, OM-10.1).
- Comparing the salient features of HIV replication and persistence across these different cellular models.
Main Results:
- Monocyte-derived macrophages (MDM) offer a model for MP infection but are limited by inter-patient variability and protocol inconsistencies.
- Cell lines like THP-1, U937, and HL-60, along with their chronically infected counterparts, provide valuable insights into HIV replication mechanisms in MP.
- These cell lines complement MDM studies, offering more standardized platforms for investigating HIV persistence and pathogenesis in MP.
Conclusions:
- Various cellular models, including MDM and specific cell lines, are essential for studying HIV infection in mononuclear phagocytes (MP).
- Each model presents unique advantages and limitations, influencing the understanding of HIV pathogenesis and viral persistence.
- Continued comparative analysis of these models is crucial for advancing research on HIV reservoirs and developing effective therapeutic strategies.
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