Differential regulation of TREM2 and CSF1R in CNS macrophages in an SIV/macaque model of HIV CNS disease

Knight, Audrey C.; Brill, Samuel A; Solis, Clarisse V.; Richardson, Morgan R.; McCarron, Megan E.; Queen, Suzanne E.; Bailey, Charles C.; Mankowski, Joseph L.

doi:10.1007/s13365-020-00844-1

Cited by 10 publications

(2 citation statements)

References 35 publications

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“…We have recently determined that in response to JHMV infection of the CNS of immunocompetent mice, there are inflammatory monocyte/macrophage subpopulations that differentially express CD115/CSF-1R and this highlights the highly inflammatory nature of these cells in models of neurodegeneration ( 37 ). Expression of CD115-expressing macrophages and microglia have also been detected in other models of neuroinflammation demonstrating important roles for these cells in contributing to inflammatory responses ( 38 – 40 ). More recently, microglia are recognized to be important in host defense in response to viral infection of the CNS ( 41 – 45 ).…”

Section: Discussionmentioning

confidence: 91%

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Olivarria

Cheng

Furman

et al. 2022

J Virol

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Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine ( Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19 ) and cytokine ( Ifn-λ and Tnf-α ) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. Importance Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

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Section: Discussionmentioning

confidence: 91%

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Olivarria

Cheng

Furman

et al. 2022

J Virol

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“…HIV can invade the central nervous system (CNS), causing neuroinflammatory immune activation and neurodegenerative alterations, resulting in HIV-related neurocognitive impairment ( Knight et al., 2018 ; Knight et al., 2020 ). Astrocytes are the most abundant cell type in CNS and play a vital role in maintaining the CNS homeostasis and regulating blood flow in response to injury and diseases ( Guttenplan and Liddelow, 2019 ).…”

Section: The Cell Reservoir Of Hivmentioning

confidence: 99%

The reservoir of latent HIV

Chen

Zhou

Zhang

et al. 2022

Front. Cell. Infect. Microbiol.

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The persistence of latent reservoir of the human immunodeficiency virus (HIV) is currently the major challenge in curing HIV infection. After HIV infects the human body, the latent HIV is unable to be recognized by the body’s immune system. Currently, the widely adopted antiretroviral therapy (ART) is also unble to eliminate it, thus hindering the progress of HIV treatment. This review discusses the existence of latent HIV vault for HIV treatment, its formation and factors affecting its formation, cell, and tissue localization, methods for detection and removing latent reservoir, to provide a comprehensive understanding of latent HIV vault, in order to assist in the future research and play a potential role in achieving HIV treatment.

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Myeloid Cell Reservoirs: Role in HIV-Host Interplay and Strategies for Myeloid Reservoir Elimination

Castillo,

McElrath,

Marshall

et al. 2024

Curr Clin Micro Rpt

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Purpose of Review Despite host antiviral responses and antiretroviral therapy, HIV-1 continues to persist in myeloid cell reservoirs. Hence, strategies that promote the elimination of myeloid reservoirs are critically needed. Insight into host-HIV interactions is key to achieving a cure. Recent Findings Host antiviral factors are often antagonized by HIV proteins that help establish infection while promoting chronic inflammation and disease in the host. Currently, several methods to eliminate the virus are under investigation including broadly neutralizing antibodies, latency reversal agents, CRISPR platforms, and immune modulation. Compounds that can penetrate the blood brain barrier are also being developed for reservoir cell clearance. Summary Here, we will outline features of myeloid cell biology and host-virus interactions that facilitate HIV persistence. We will also review current therapeutic strategies and potential drug candidates to cure HIV infection of myeloid cells even in difficult-to-treat tissues such as the central nervous system.

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Differential regulation of TREM2 and CSF1R in CNS macrophages in an SIV/macaque model of HIV CNS disease

Cited by 10 publications

References 35 publications

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

The reservoir of latent HIV

Myeloid Cell Reservoirs: Role in HIV-Host Interplay and Strategies for Myeloid Reservoir Elimination

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