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HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

  • Jonathan Herskovitz
  • Howard E. Gendelman
INVITED REVIEW

Abstract

Macrophages serve as host cells, inflammatory disease drivers and drug runners for human immunodeficiency virus infection and treatments. Low-level viral persistence continues in these cells in the absence of macrophage death. However, the cellular microenvironment changes as a consequence of viral infection with aberrant production of pro-inflammatory factors and promotion of oxidative stress. These herald viral spread from macrophages to neighboring CD4+ T cells and end organ damage. Virus replicates in tissue reservoir sites that include the nervous, pulmonary, cardiovascular, gut, and renal organs. However, each of these events are held in check by antiretroviral therapy. A hidden and often overlooked resource of the macrophage rests in its high cytoplasmic nuclear ratios that allow the cell to sense its environment and rid it of the cellular waste products and microbial pathogens it encounters. These phagocytic and intracellular killing sensing mechanisms can also be used in service as macrophages serve as cellular carriage depots for antiretroviral nanoparticles and are able to deliver medicines to infectious disease sites with improved therapeutic outcomes. These undiscovered cellular functions can lead to reductions in persistent infection and may potentially facilitate the eradication of residual virus to eliminate disease.

Keywords

Mononuclear phagocytes Monocyte-derived macrophages Human immunodeficiency virus Viral persistence Long acting slow effective release antiretroviral therapy Cell ontogeny Viral reservoirs 

Notes

Acknowledgments

We thank Drs. Benson Edagwa and Aditya Bade for their thoughtful discussions. This work was supported in part by NIH Grants R01 AG043540, P01 DA028555, P30 MH062261, R01 MH115860, R01 NS034239, R01 NS036126, and the Carol Swartz Emerging Neuroscience Fund.

Compliance with Ethical Standards

Conflict of Interest

None.

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Authors and Affiliations

  1. 1.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical CenterOmahaUSA

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