Article
Microbiology
Rosiris Leon-Rivera, Mike Veenstra, Maribel Donoso, Elizabeth Tell, Eliseo A. Eugenin, Susan Morgello, Joan W. Berman
Summary: This study demonstrates that monocytes from people living with HIV on suppressive cART can carry integrated HIV and preferentially cross the blood-brain barrier, contributing to the establishment of CNS viral reservoirs. Additionally, the study proposes potential therapeutic targets to inhibit this transmigration process and prevent CNS reservoir replenishment.
Review
Immunology
Michelle K. Ash, Lena Al-Harthi, Jeffrey R. Schneider
Summary: Advances in antiretroviral therapy have prolonged the lives of people living with HIV by reducing viral levels, but challenges remain in eradicating the virus due to significant reservoirs in the central nervous system. Astraycytes and microglia in the CNS have been shown to harbor HIV even with treatment, emphasizing the need for optimization of curative strategies. Measuring the latent HIV reservoir and addressing neuroinflammation in the brain are crucial in developing effective treatment options for HIV-associated neurocognitive disorders.
Article
Medicine, Research & Experimental
Shelli F. Farhadian, Ofir Lindenbaum, Jun Zhao, Michael J. Corley, Yunju Im, Hannah Walsh, Alyssa Vecchio, Rolando Garcia-Milian, Jennifer Chiarella, Michelle Chintanaphol, Rachela Calvi, Guilin Wang, Lishomwa C. Ndhlovu, Jennifer Yoon, Diane Trotta, Shuangge Ma, Yuval Kluger, Serena Spudich
Summary: People with HIV on antiretroviral therapy experience neurological impairment, possibly due to viral or neuroimmune causes. Single-cell analysis of paired cerebrospinal fluid and peripheral blood revealed the production of HIV-1 RNA in central memory CD4+ T cells in the cerebrospinal fluid, as well as a higher frequency of infected cells in the cerebrospinal fluid compared to the blood. Additionally, rare microglia-like cells in the cerebrospinal fluid were identified using a reliable cell surface marker, CD204. Abnormal CD8+ T cell activation was found to be prevalent in the cerebrospinal fluid of people with HIV, suggesting ongoing CNS viral persistence and compartmentalized neuroimmune effects.
Article
Immunology
Aniella J. Murphy, Jennifer Kelschenbach, Hongxia He, Wei Chao, Boe-Hyun Kim, David J. Volsky, Joan W. Berman
Summary: Thirty-eight million people worldwide are living with HIV, a major public health problem. Antiretroviral therapy revolutionized HIV treatment and significantly increased the lifespan of people with HIV. However, 15-50% of people with HIV develop HIV associated neurocognitive disorders, which negatively impact quality of life. Many people with HIV also have opioid use disorder, and studies suggest that opioid use disorder can contribute to HIV neurocognitive disorders. The effects of buprenorphine, a synthetic opioid agonist used to treat opioid use disorder, on HIV neurocognitive disorders are unclear. This study found that buprenorphine treatment can reverse chronic neurocognitive impairment in mice with HIV infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Alexander O. Pasternak, Christina K. Psomas, Ben Berkhout
Summary: Combination antiretroviral therapy suppresses HIV replication and improves immune function, but therapy interruption often leads to rapid viral rebound due to the persistence of long-lived HIV reservoirs. A small percentage of individuals who can control HIV replication for extended periods without therapy represent potential models for long-term HIV remission, but most individuals with a low viral reservoir still experience fast viral rebound.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Sarah E. Benner, Xianming Zhu, Sarah Hussain, Sander Florman, Yolanda Eby, Reinaldo E. Fernandez, Darin Ostrander, Meenakshi Rana, Shane Ottmann, Jonathan Hand, Jennifer C. Price, Marcus R. Pereira, David Wojciechowski, Jacques Simkins, Valentina Stosor, Sapna A. Mehta, Saima Aslam, Maricar Malinis, Ghady Haidar, Allan Massie, Melissa L. Smith, Jonah Odim, Megan Morsheimer, Thomas C. Quinn, Gregory M. Laird, Robert Siliciano, Ashwin Balagopal, Dorry L. Segev, Christine M. Durand, Andrew D. Redd, Aaron A. R. Tobian
Summary: We investigated the impact of receiving a liver transplant on the HIV latent viral reservoir (LVR). LVR did not show any changes in recipients with HIV who received a liver from HIV-positive or HIV-negative donors. The stability of LVR after liver transplantation in people with HIV indicates its importance as a barrier to HIV-1 cure strategies.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Virology
Hailong Li, Kristen A. McLaurin, Charles F. Mactutus, Benjamin Likins, Wenfei Huang, Sulie L. Chang, Rosemarie M. Booze
Summary: The prevalence of HIV-1 associated neurocognitive disorders (HAND) is higher in older individuals, and using HIV-1 Tg rats as a model, researchers found abnormal beta-amyloid accumulation in the prefrontal cortex and hippocampus, suggesting a potential mechanism underlying synaptodendritic damage in HAND.
Article
Neurosciences
Xiaolei Zhu, Kristen R. Hollinger, Alejandra Borjabad, Boe-Hyun Kim, Tanina Arab, Ajit G. Thomas, Mohammed Moniruzzaman, Lyndah Lovell, Andrey Turchinovich, Kenneth W. Witwer, David J. Volsky, Norman J. Haughey, Barbara S. Slusher
Summary: People living with HIV often have cognitive impairment and major depressive disorder. Inhibiting the enzyme neutral sphingomyelinase 2 may be a new therapeutic strategy for treating these disorders.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Medicine, Research & Experimental
Bingfeng Liu, Wanying Zhang, Baijin Xia, Shuliang Jing, Yingying Du, Fan Zou, Rong Li, Lijuan Lu, Shaozhen Chen, Yonghong Li, Qifei Hu, Yingtong Lin, Yiwen Zhang, Zhangping He, Xu Zhang, Xiejie Chen, Tao Peng, Xiaoping Tang, Weiping Cai, Ting Pan, Linghua Li, Hui Zhang
Summary: This study investigated the safety and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 undergoing analytical interruption of antiretroviral therapy. The therapy was found to be safe and effective, reducing viral reservoir, but rebound was due to viral escape mutations.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Immunology
Jarrod York, Kavitha Gowrishankar, Kenneth Micklethwaite, Sarah Palmer, Anthony L. Cunningham, Najla Nasr
Summary: Despite the effectiveness of ART in reducing morbidity and mortality associated with HIV infection, the latent HIV reservoir remains a major barrier to immune clearance and HIV cure. CAR T cell therapies, involving genetically engineered T cells, offer promising potential in targeting HIV-infected cells and have shown efficacy, safety, and long-term persistence in peripheral blood.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Paula Beltran-Lobo, Martina M. Hughes, Claire Troakes, Cara L. Croft, Huzefa Rupawala, Daniel Jutzi, Marc-David Ruepp, Maria Jimenez-Sanchez, Michael S. Perkinton, Michael Kassiou, Todd E. Golde, Diane P. Hanger, Alexei Verkhratsky, Beatriz G. Perez-Nievas, Wendy Noble
Summary: P2X7R protein levels increase in AD brain, correlating with advancing Braak stage and synapse loss. P2X7R is expressed in microglia and astrocytes and is involved in the modulation of inflammation and cytokine production. Inhibition of P2X7R reduces insoluble tau levels, indicating a non-cell autonomous role of glial P2X7R in pathological tau aggregation.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Medicine, General & Internal
Paula Martinez-Roman, Celia Crespo-Bermejo, Daniel Valle-Millares, Violeta Lara-Aguilar, Sonia Arca-Lafuente, Luz Martin-Carbonero, Pablo Ryan, Ignacio de los Santos, Maria Rosa Lopez-Huertas, Claudia Palladino, Maria Munoz-Munoz, Amanda Fernandez-Rodriguez, Mayte Coiras, Veronica Briz
Summary: This study found that the elimination of hepatitis C virus (HCV) using direct-acting antivirals (DAAs) did not modify the HIV reservoir and viral splicing. Additionally, individuals who spontaneously cleared HCV showed a significant decrease in the HIV reservoir, possibly due to an enhanced immune response.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Agnes Dombi, Csenge Santa, Istvan Z. Batai, Viktoria Kormos, Angela Kecskes, Valeria Tekus, Krisztina Pohoczky, Kata Bolcskei, Erika Pinter, Gabor Pozsgai
Summary: The study found that dimethyl trisulfide (DMTS) can alleviate neuropathic pain through TRPA1 ion channels and SST4 receptors, but is ineffective in mice lacking both. DMTS does not affect macrophage activity around damaged nerves, but can reduce the density of microglia in the spinal cord dorsal horn.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Marine Baron, Cathia Soulie, Armelle Lavole, Lambert Assoumou, Baptiste Abbar, Baptiste Fouquet, Alice Rousseau, Marianne Veyri, Assia Samri, Alain Makinson, Sylvain Choquet, Julien Mazieres, Solenn Brosseau, Brigitte Autran, Dominique Costagliola, Christine Katlama, Jacques Cadranel, Anne-Genevieve Marcelin, Olivier Lambotte, Jean-Philippe Spano, Amelie Guihot
Summary: The study suggests that ICP blockade could be a potential therapeutic strategy for HIV cure. Anti-PD-1 therapy showed a decrease in HIV-DNA, but no significant increase in HIV-specific immunity. It was observed that there was an early increase in CTLA-4+ CD4+ T cells and a greater increase in CTLA-4+ and TIM-3+ CD8+ T cells in patients without HIV-DNA reduction.
Article
Microbiology
Maura Statzu, Guido Silvestrl
Summary: Cytotoxic CD8(+) T cells can decrease the lifespan of infected cells during acute simian immunodeficiency virus infection, but they are unable to prevent the establishment of a persistent reservoir of latently infected cells under long-term antiretroviral therapy.
NATURE MICROBIOLOGY
(2023)
Article
Neurosciences
Kristen A. McLaurin, Rosemarie M. Booze, Charles F. Mactutus
JOURNAL OF NEUROVIROLOGY
(2019)
Article
Multidisciplinary Sciences
Hailong Li, Jessica M. Illenberger, Michael N. Cranston, Charles F. Mactutus, Kristen A. McLaurin, Steven B. Harrod, Rosemarie M. Booze
Article
Multidisciplinary Sciences
Kristen A. McLaurin, Hailong Li, Rosemarie M. Booze, Charles F. Mactutus
SCIENTIFIC REPORTS
(2019)
Article
Neurosciences
Adam R. Denton, Srimal A. Samaranayake, Kristin N. Kirchner, Robert F. Roscoe, Shane N. Berger, Steven B. Harrod, Charles F. Mactutus, Parastoo Hashemi, Rosemarie M. Booze
JOURNAL OF NEUROVIROLOGY
(2019)
Article
Multidisciplinary Sciences
Kristen A. McLaurin, Landhing M. Moran, Hailong Li, Rosemarie M. Booze, Charles F. Mactutus
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2019)
Review
Neurosciences
Jessica M. Illenberger, Steven B. Harrod, Charles F. Mactutus, Kristen A. McLaurin, Asha Kallianpur, Rosemarie M. Booze
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2020)
Correction
Neurosciences
Jessica M. Illenberger, Steven B. Harrod, Charles F. Mactutus, Kristen A. McLaurin, Asha Kallianpur, Rosemarie M. Booze
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2020)
Article
Neurosciences
Adam R. Denton, Charles F. Mactutus, Almeera U. Lateef, Steven B. Harrod, Rosemarie M. Booze
Summary: The study found that SSRI treatment can restore behavioral impairments and synaptodendritic damage caused by HIV-1, but may not consistently be effective at the neurochemical level.
JOURNAL OF NEUROVIROLOGY
(2021)
Review
Cell Biology
Kristen A. McLaurin, Michael Harris, Victor Madormo, Steven B. Harrod, Charles F. Mactutus, Rosemarie M. Booze
Summary: This review critically examines the evidence for dopaminergic alterations following chronic exposure to HIV-1 viral proteins, concluding that long-term exposure leads to decreased dopamine function despite the use of combination antiretroviral therapy. It highlights the importance of focusing on strategies to rectify decreases in dopamine function for effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments.
Article
Cell Biology
Kristen A. McLaurin, Hailong Li, Rosemarie M. Booze, Charles F. Mactutus
Summary: The study found that HIV infection can cause neurocognitive impairments in perinatally infected adolescents, primarily due to synaptodendritic dysfunction rather than early neuroinflammation. This study reveals the impact mechanism of HIV-1 on brain development.
Article
Biochemistry & Molecular Biology
Kristen A. McLaurin, Hailong Li, Charles F. Mactutus, Steven B. Harrod, Rosemarie M. Booze
Summary: Chronic cocaine use and HIV-1 viral protein exposure independently lead to neuroadaptations in the frontal-striatal circuit. However, the response of the frontal-striatal circuit to HIV-1 infection following chronic drug use has been unclear. A study using rats found that male rats preferred cocaine while female rats preferred sucrose. Regardless of biological sex, inoculation with chimeric HIV disrupted decision-making and resulted in structural alterations in the frontal-striatal circuit.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)