Article
Immunology
Tingxia Lv, Wei Cao, Jing Xue, Qiang Wei, Zhifeng Qiu, Yang Han, Taisheng Li
Summary: LLDT-8 administration during chronic SIV infection did not have a significant effect on T cell activation and viral rebound.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Marina McDew-White, Eunhee Lee, Xavier Alvarez, Karol Sestak, Binhua J. Ling, Siddappa N. Byrareddy, Chioma M. Okeoma, Mahesh Mohan
Summary: This study provides insights into the molecular mechanisms of HIV/SIV-induced periodontal disease and highlights the anti-inflammatory and anti-dysbiotic properties of phytocannabinoids. These findings are important for people living with HIV who are on antiretroviral therapy, as phytocannabinoids may help control the progression of the disease.
Article
Immunology
Xiaosheng Liu, Tingxia Lv, Xiuxia Li, Jing Xue, Ling Lin, Lianfeng Lu, Xiaodi Li, Yang Yang, Yuanni Wu, Qiang Wei, Wei Cao, Taisheng Li
Summary: LLDT-8 exhibits notable efficacy in alleviating immune activation in both an in vivo animal model and in vitro human cell experiments, suggesting its potential as a drug for managing systemic immune activation associated with SIV/HIV infection.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Mary S. Pampusch, Emily N. Sevcik, Zoe E. Quinn, Brianna C. Davey, James M. Berg, Ian Gorrell-Brown, Hadia M. Abdelaal, Eva G. Rakasz, Aaron Rendahl, Pamela J. Skinner
Summary: This study found that SIV-infected rhesus macaques treated with CXCR5-expressing SIV-specific CD4-MBL-CAR-T cells showed reduced viral loads. The temporary disruption of lymphoid follicles increased the abundance and persistence of CAR-T cells. These findings have important implications for the development of cellular immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Chunxiu Wu, Jin Zhao, Ruiting Li, Fengling Feng, Yizi He, Yanjun Li, Runhan Huang, Guangye Li, Heng Yang, Genhong Cheng, Ling Chen, Feng Ma, Pingchao Li, Caijun Sun
Summary: The combination of 25HC with antiretroviral therapy was found to provide profound immunological modulation in chronically SIV-infected rhesus macaques, inhibiting viral replication, enhancing cellular immune responses, and restoring immune cell ratios. Assessments also highlighted the relationship between cholesterol metabolism, immune modulation, and antiviral activities of 25HC, offering insight for potential therapeutic drug candidates against HIV-1 and related diseases.
Article
Immunology
Nongthombam Boby, Apurv Srivastav, Sudesh K. Srivastav, Bapi Pahar
Summary: Cytokine and chemokine levels are significant predictive factors of HIV pathogenesis and disease outcome. Evaluating cytokine and chemokine levels during acute infection can help identify critical changes and improve HIV treatment and prevention methods. In a rhesus macaque model, 11 cytokines/growth factors and 9 chemokines showed substantial changes during acute infection. IL-18, IP-10, FLT3L, MCP-1, MCP-2, and MIP-3 beta were identified as biomarkers for predicting CD4+ T cell loss and viral replication during acute SIV/HIV infection.
Article
Immunology
Nichole R. Klatt, Courtney Broedlow, Jessica M. Osborn, Andrew T. Gustin, Sandra Dross, Megan A. O'Connor, Ernesto Coronado, Philip Barnette, Tiffany Hensley-McBain, Alexander S. Zevin, Roshell Muir, Alexander Roederer, Solomon Wangari, Naoto Iwayama, Chul Y. Ahrens, Jeremy Smedley, Cassandra Moats, Rebecca M. Lynch, Elias K. Haddad, Nancy L. Haigwood, Deborah H. Fuller, Jennifer A. Manuzak
Summary: Although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.
Article
Immunology
Brianna C. Davey, Mary S. Pampusch, Emily K. Cartwright, Hadia M. Abdelaal, Eva G. Rakasz, Aaron Rendahl, Edward A. Berger, Pamela J. Skinner
Summary: T cells expressing a SIV-specific chimeric antigen receptor (CAR) and CXCR5 were infused into SIV-infected rhesus macaques on antiretroviral therapy (ART) to assess their ability to control the virus. These cells showed evidence of functionality but failed to persist in the animals beyond 28 days, possibly due to the development of anti-CAR antibodies. The study suggests that the CD4 and CD28 domains of the CAR are immunogenic and could impact the long-term persistence of CAR immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Bapi Pahar, Wayne Gray, Marissa Fahlberg, Brooke Grasperge, Meredith Hunter, Arpita Das, Christopher Mabee, Pyone Pyone Aye, Faith Schiro, Krystle Hensley, Aneeka Ratnayake, Kelly Goff, Celia LaBranche, Xiaoying Shen, Georgia D. Tomaras, C. Todd DeMarco, David Montefiori, Patricia Kissinger, Preston A. Marx, Vicki Traina-Dorge
Summary: By using a varicella virus-vectored SIV vaccine and protein boosts, this study demonstrated a 37.5% efficacy rate against pathogenic SIV challenge in a rhesus macaque model by generating neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses.
Article
Immunology
Sabrina Helmold Hait, Christopher James Hogge, Mohammad Arif Rahman, Ruth Hunegnaw, Zuena Mushtaq, Tanya Hoang, Marjorie Robert-Guroff
Summary: T follicular helper (T-FH) cells play a crucial role in B cell affinity maturation in lymph nodes. Meanwhile, circulating CXCR5(+) CD4(+) T (cT(FH)) cells support memory B cell activation and broadly neutralizing antibodies in HIV controllers. This study investigated the contribution of LN SIV-specific T-FH and cT(FH) cells to Env-specific humoral immunity in female rhesus macaques under different vaccination and SIV challenge conditions, revealing the importance of T-FH responses in blood and secondary lymphoid organs for protective efficacy of HIV vaccines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Nongthombam Boby, Xuewei Cao, Kelsey Williams, Shiva Kumar Goud Gadila, Monica N. Shroyer, Peter J. Didier, Sudesh K. Srivastav, Arpita Das, Kate Baker, Qiuying Sha, Bapi Pahar
Summary: The expression of ACE2 and RAS-associated proteins may be compromised after SIV/HIV infection, leading to the loss of gut homeostasis and aggravated pathological events.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sharat Srinivasula, Paula Degrange, Simone Perazzolo, Andrew Bonvillain, Amanda Tobery, Jacob Kaplan, Hyukjin Jang, Refika Turnier, Michael Davies, Mackenzie Cottrell, Rodney J. Y. Ho, Michele Di Mascio
Summary: This study investigates the relationship between immunovirological factors and antiretroviral (ARV) drug levels in lymph nodes (LN) during HIV therapy. The results show that intracellular active drug-metabolite (IADM) levels in lymph node mononuclear cells (LNMC) are significantly lower than in peripheral blood mononuclear cells (PBMC). The levels of IADM increase in both LNMC and PBMC over time, with a steeper increase in LNMC. There is a negative correlation between viral dissemination and IADM levels at the start of antiretroviral therapy. Simulation models suggest that reduced immune activation improves the formation of active drug-metabolites. These findings have implications for the efficacy of antiviral therapies targeting pathogenic viruses in highly inflammatory anatomical compartments.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Nongthombam Boby, Xuewei Cao, Alyssa Ransom, Barcley T. Pace, Christopher Mabee, Monica N. Shroyer, Arpita Das, Peter J. Didier, Sudesh K. Srivastav, Edith Porter, Qiuying Sha, Bapi Pahar
Summary: Research has shown that under SIV infection, intestinal epithelial regeneration decreases, certain cell types increase, and differentially expressed genes in important pathways are downregulated. Despite the lack of significant reduction in stem cell population, dysregulation of intestinal stem cell niche factors, presence of inflammatory factors, and loss of epithelial barrier function, suggest that SIV infection impacts epithelial cell proliferation and intestinal homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Chase E. Hawes, Sonny R. Elizaldi, Danielle Beckman, Giovanne B. Diniz, Yashavanth Shaan Lakshmanappa, Sean Ott, Blythe P. Durbin-Johnson, Ashok R. Dinasarapu, Andrea Gompers, John H. Morrison, Smita S. Iyer
Summary: Research highlights the immune surveillance of the rhesus CNS by innate and adaptive immune cells during homeostasis. Following SHIV infection, vulnerabilities of key cognitive and motor function brain regions to HIV-1 during the acute phase were demonstrated by viral entry and integration within multiple brain regions.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Multidisciplinary Sciences
Victoria E. K. Walker-Sperling, Noe B. Mercado, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Mark Lewis, Jeffrey P. Murry, Yunling Yang, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael, Maria G. Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. Siliciano, Dan H. Barouch
Summary: This study suggests that combining active and passive immunization may have the potential in curing HIV-1. In SHIV-infected rhesus macaques, a combination of therapeutic vaccination and antibody administration with vesatolimod resulted in 70% post-ART virologic control.
NATURE COMMUNICATIONS
(2022)
Article
Substance Abuse
Erika M. Rosen, Stefany D. Primeaux, Liz Simon, David A. Welsh, Patricia E. Molina, Tekeda F. Ferguson
Summary: The study found that binge drinking and heavy alcohol use were associated with increased calorie and fat intake among people living with HIV, but binge drinkers were less likely to consume a high-sugar diet. Interventions focused on reducing alcohol use and promoting lower energy-dense foods with reduced fat may be beneficial in reducing metabolic disease burden in this population.
ALCOHOL AND ALCOHOLISM
(2022)
Review
Substance Abuse
Natalia A. Osna, Moses New-Aaron, Raghubendra S. Dagur, Paul Thomes, Liz Simon, Danielle Levitt, Patrick McTernan, Patricia E. Molina, Hye Yeon Choi, Keigo Machida, Kenneth E. Sherman, Antonio Riva, Sandra Phillips, Shilpa Chokshi, Kusum K. Kharbanda, Steven Weinman, Murali Ganesan
Summary: The article discusses the exacerbating effects of alcohol on viral infections and the underlying mechanisms, focusing on the immune and metabolic changes in hepatotropic viral infections, as well as the interactions between viruses and alcohol.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Review
Physiology
Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
Summary: At-risk alcohol use contributes significantly to the global healthcare burden, leading to preventable diseases and deaths. Understanding the mechanisms of alcohol-induced tissue injury is crucial for the development of effective interventions. This article provides a comprehensive review of the current knowledge on the pathophysiological mechanisms involved in alcohol-related tissue damage.
ANNUAL REVIEW OF PHYSIOLOGY
(2022)
Article
Critical Care Medicine
Alejandra Jacotte-Simancas, Jason W. Middleton, Zachary F. Stielper, Scott Edwards, Patricia E. Molina, Nicholas W. Gilpin
Summary: TBI produces sex-specific acute effects on BLA neuronal activation, excitability, and synaptic transmission. Females exhibit increased apnea duration and reduced respiratory rate post-TBI relative to males. In both male and female rats, TBI increases c-fos expression in BLA glutamatergic cells and firing rate in BLA pyramidal neurons. In females, TBI also increases spontaneous excitatory and inhibitory postsynaptic current amplitude and sEPSC frequency in BLA neurons.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Substance Abuse
Brianna L. Bourgeois, Danielle E. Levitt, Patricia E. Molina, Liz Simon
Summary: Our studies demonstrate that chronic binge alcohol (CBA) and HIV infection significantly impact metabolic homeostasis, particularly in adipose tissue and skeletal muscle. CBA alters the differentiation potential of adipose-derived stem cells and myoblasts, and the differential expression of microRNAs (miRs) contributes to impaired myoblast differentiation. CBA also modulates the concentration and miR cargo of extracellular vesicles (EVs) derived from adipocytes and myotubes in SIV-infected macaques. These findings underscore the importance of EV-mediated intercellular communication in metabolic dysregulation.
Article
Immunology
Nongthombam Boby, Apurv Srivastav, Sudesh K. Srivastav, Bapi Pahar
Summary: Cytokine and chemokine levels are significant predictive factors of HIV pathogenesis and disease outcome. Evaluating cytokine and chemokine levels during acute infection can help identify critical changes and improve HIV treatment and prevention methods. In a rhesus macaque model, 11 cytokines/growth factors and 9 chemokines showed substantial changes during acute infection. IL-18, IP-10, FLT3L, MCP-1, MCP-2, and MIP-3 beta were identified as biomarkers for predicting CD4+ T cell loss and viral replication during acute SIV/HIV infection.
Article
Endocrinology & Metabolism
Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. McDaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J. J. Ronis
Summary: This study examines the relationship between alcohol use, bone health, and bone mass changes in people living with HIV. Through clinical data and animal experiments, the study findings suggest that alcohol consumption is associated with alterations in bone morphology and density, and age and menopausal status increase the susceptibility to these effects.
Article
Immunology
Michael G. Dubic, Scott Edwards, Lee S. McDaniel, Liz Simon, Patricia E. Molina
Summary: People living with HIV are more likely to engage in risky alcohol use and are at higher risk of neurocognitive decline. This study explored the mechanisms underlying HIV-associated neurocognitive disorder (HAND) and found that chronic binge alcohol consumption may increase neuroinflammatory gene expression and decrease growth factor signaling. Additionally, gene expression patterns in peripheral blood mononuclear cells (PBMCs) may reflect expression changes in the brain. These findings are important for understanding HAND related to alcohol use and HIV exposure.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2023)
Review
Biochemistry & Molecular Biology
Robert W. Siggins, Patrick M. McTernan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
Summary: Alcohol misuse negatively affects tissues involved in energy metabolism regulation, such as the liver, pancreas, adipose, and skeletal muscle. It impairs mitochondrial functions and disrupts immunometabolism, leading to tissue injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
David X. Liu, Bapi Pahar, Timothy K. Cooper, Donna L. Perry, Huanbin Xu, Louis M. Huzella, Ricky D. Adams, Amanda M. W. Hischak, Randy J. Hart, Rebecca Bernbaum, Deja Rivera, Scott Anthony, Marisa St Claire, Russell Byrum, Kurt Cooper, Rebecca Reeder, Jonathan Kurtz, Kyra Hadley, Jiro Wada, Ian Crozier, Gabriella Worwa, Richard S. Bennett, Travis Warren, Michael R. Holbrook, Connie S. Schmaljohn, Lisa E. Hensley
Summary: In this study, the researchers found that rhesus monkeys infected with the Ebola virus exhibit pathophysiological features similar to hemophagocytic lymphohistiocytosis syndrome/macrophage activation syndrome. Therefore, regulating inflammation and immune function may provide an effective treatment for controlling the pathogenesis of acute Ebola virus disease.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Medicine, Research & Experimental
Flavia M. Souza-Smith, Patricia E. Molina, Rajani Maiya
Summary: Chronic alcohol consumption in rodents leads to hyperpermeability of mesenteric collecting lymphatic vessels, lymph leakage, and immunometabolic dysregulation of perilymphatic adipose tissue (PLAT). This study aimed to investigate the alcohol-induced changes in lymph and plasma proteome using quantitative proteomic analysis. The results identified upregulation of apolipoproteins in lymph from alcohol-fed animals and downregulation of proteins in the plasma of alcohol-fed animals. Network analysis also revealed differentially expressed hub proteins in the lymph, while plasma analysis showed a module with no significant enrichment of differentially expressed proteins. Further studies will explore the functionality of these hub proteins in both lymph and plasma.
Article
Multidisciplinary Sciences
Ivy Phung, Kristen A. Rodrigues, Ester Marina-Zarate, Laura Maiorino, Bapi Pahar, Wen-Hsin Lee, Mariane Melo, Amitinder Kaur, Carolina Allers, Marissa Fahlberg, Brooke F. Grasperge, Jason P. Dufour, Faith Schiro, Pyone P. Aye, Paul G. Lopez, Jonathan L. Torres, Gabriel Ozorowski, Saman Eskandarzadeh, Michael Kubitz, Erik Georgeson, Bettina Groschel, Rebecca Nedellec, Michael Bick, Katarzyna Kaczmarek Michaels, Hongmei Gao, Xiaoying Shen, Diane G. Carnathan, Guido Silvestri, David C. Montefiori, Andrew B. Ward, Lars Hangartner, Ronald S. Veazey, Dennis R. Burton, William R. Schief, Darrell J. Irvine, Shane Crotty
Summary: The study explores a combined adjuvant approach using pSer:alum-mediated antigen delivery and potent adjuvants, which enhances humoral immune responses by modulating immunodominance. The findings show promise for clinical translation and highlight the importance of adjuvants and antigen delivery kinetics in rational vaccine design.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliu, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson
Summary: Chronic alcohol abuse leads to alterations in the gastrointestinal microbiota, resulting in behavior changes, physiological alterations, and immunological effects. This study developed a humanized alcohol-microbiota mouse model and found that colonization of mice with fecal microbiota from individuals with high AUDIT scores increased susceptibility to pneumonia.
Article
Substance Abuse
Shawn M. Cohen, Dominick Dephilippis, Yanhong Deng, James Dziura, Tekeda Ferguson, Lisa M. Fucito, Amy C. Justice, Stephen Maisto, Vincent C. Marconi, Patricia Molina, Manuel Paris, Maria C. Rodriguez-Barradas, Michael Simberkoff, Nancy M. Petry, David A. Fiellin, E. Jennifer Edelman
Summary: This study evaluated perspectives on implementing contingency management (CM) to address unhealthy alcohol use for people with HIV in primary care settings. CM was viewed as a helpful, positive, and feasible approach to addressing unhealthy alcohol use and related conditions among patients and staff involved in a clinical trial. To enhance implementation, future efforts may consider simplified approaches to the reward structure and expanding rewards to non-abstinent reductions in alcohol consumption.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Review
Cell Biology
Liz Simon, Patricia E. Molina
Summary: At-risk alcohol use has significant effects on multiple organ systems and causes global health burden. Alcohol interferes with bioenergetic pathways in tissues, leading to cellular injury. This review focuses on the alcohol-induced bioenergetic adaptations in metabolically active tissues, such as the liver, heart, skeletal muscle, pancreas, and brain.