Shock and kill within the CNS: A promising HIV eradication approach?

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Marieke M. Nühn¹  Stephanie B. H. Gumbs¹  Ninée V. E. J. Buchholtz¹  Lisanne M. Jannink¹  Lavina Gharu¹  Lot D. de Witte¹  Annemarie M. J. Wensing¹  Sharon R. Lewin³  Monique Nijhuis¹  Jori Symons¹ 

[1] Translational Virology, Department of Medical Microbiology, University Medical Center;Department of Psychiatry, Icahn School of Medicine;Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute of Immunity and Infection;Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute of Immunity and Infection;Department of Infectious Diseases, Alfred Hospital and Monash University

关键词: astrocytes;    CNS;    compartmentalization;    eradication;    HAND;    HIV;    inflammation;    latency;    latency reversal;    microglia;    perivascular macrophages;    persistence;    reservoir;    shock and kill;   

DOI  :  10.1002/JLB.5VMR0122-046RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The most studied HIV eradication approach is the “shock and kill” strategy, which aims to reactivate the latent reservoir by latency reversing agents (LRAs) and allowing elimination of these cells by immune-mediated clearance or viral cytopathic effects. The CNS is an anatomic compartment in which (persistent) HIV plays an important role in HIV-associated neurocognitive disorder. Restriction of the CNS by the blood–brain barrier is important for maintenance of homeostasis of the CNS microenvironment, which includes CNS-specific cell types, expression of transcription factors, and altered immune surveillance. Within the CNS predominantly myeloid cells such as microglia and perivascular macrophages are thought to be a reservoir of persistent HIV infection. Nevertheless, infection of T cells and astrocytes might also impact HIV infection in the CNS. Genetic adaptation to this microenvironment results in genetically distinct, compartmentalized viral populations with differences in transcription profiles. Because of these differences in transcription profiles, LRAs might have different effects within the CNS as compared with the periphery. Moreover, reactivation of HIV in the brain and elimination of cells within the CNS might be complex and could have detrimental consequences. Finally, independent of activity on latent HIV, LRAs themselves can have adverse neurologic effects. We provide an extensive overview of the current knowledge on compartmentalized (persistent) HIV infection in the CNS and on the “shock and kill” strategy. Subsequently, we reflect on the impact and promise of the “shock and kill” strategy on the elimination of persistent HIV in the CNS.

【 授权许可】

CC BY