Role of macrophages in HIV infection and persistence

Abstract

Current antiretroviral therapy regimens can effectively suppress HIV in patients for prolonged periods of time, but do not constitute a cure, since they are incapable of eradicating viral reservoirs. It is, therefore, necessary for us to refocus on the partially understood pathogenesis of HIV, on the issue of viral persistence, and on the development of strategies for a temporally contained therapy capable of purging HIV from the body. Macrophages play a pivotal role in all three of these scenarios. This review summarizes important aspects of macrophage biology as they relate to HIV and discusses conceptual challenges for virus suppression and eradication in this cell type. We highlight a number of significant recent advances in understanding differences in HIV replication and pharmacotherapy between macrophages and CD4 T cells, as well as the role of macrophages in various aspects of the disease process and in different anatomical compartments. Finally, the importance of infected macrophages in the persistence of HIV, regarding both pathogenesis and advancement of eradication strategies, is discussed.

Keywords::

• CNS
• compartmentalization
• eradication
• HAART
• HIV pathogenesis
• HIV replication
• immune dysfunction
• lentiviruses
• macrophage development
• sanctuaries

Acknowledgements

We are grateful to Valerie Bosch, Oliver T Fackler, Prerana Jayakumar, Jason F Kreisberg and Nico Michel for comments on the manuscript. We acknowledge financial support for Oliver T Keppler from SFB 544-B17, DFG grant Ke 742/2, subcontract R0051-B from the J David Gladstone Institutes, and from the European TRIoH consortium (EU project LSGH-2003–503480).