Article
Biochemistry & Molecular Biology
Kee-Pyo Kim, Jinmi Choi, Juyong Yoon, Jan M. Bruder, Borami Shin, Jonghun Kim, Marcos J. Arauzo-Bravo, Dong Han, Guangming Wu, Dong Wook Han, Johnny Kim, Patrick Cramer, Hans R. Schoeler
Summary: A chemical screen targeting major epigenetic pathways can identify permissive epigenetic states that enhance reprogramming competence of transcription factors. In this study, inhibiting specific epigenetic roadblocks simultaneously was found to dramatically improve the reprogramming ability of most OCT factors and enable dismantling species-dependent reprogramming competence of certain transcription factors such as OCT6.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Immunology
Zhuo Wang, Xiaowan Yin, Meichen Ma, Hongchi Ge, Bin Lang, Hong Sun, Sijia He, Yajing Fu, Yu Sun, Xiaowen Yu, Zining Zhang, Hualu Cui, Xiaoxu Han, Junjie Xu, Haibo Ding, Zhenxing Chu, Hong Shang, Yuntao Wu, Yongjun Jiang
Summary: The study revealed the important role of IP-10 in establishing HIV reservoirs in CD4+ T cells, with elevated plasma IP-10 levels being positively correlated with HIV viral load and reservoir size. Through enhancing cofilin activity and actin dynamics, IP-10 facilitated latent HIV infection of resting CD4+ T cells, while therapeutic targeting of IP-10 could potentially be a strategy to inhibit HIV latent infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Quynh P. Nguyen, Kennidy K. Takehara, Tianda Z. Deng, Shannon O'Shea, Maximilian Heeg, Kyla D. Omilusik, J. Justin Milner, Sara Quon, Matthew E. Pipkin, Jinyong Choi, Shane Crotty, Ananda W. Goldrath
Summary: After infection, T cells differentiate into long-lived memory cells that can circulate through secondary lymphoid organs or reside in tissues. CD4+ tissue-resident memory T cells (TRM) in the small intestine (SI) responding to acute viral infection share a gene expression program and chromatin accessibility profile with circulating TH1 cells, and gradually acquire a mature TRM program. Single-cell RNA sequencing reveals heterogeneity among established CD4+ TRM, predominantly located in the lamina propria, and identifies a population of cells that coexpress both effector- and memory-associated genes. Transcriptional regulators Blimp1, Id2, and Bcl6 are required for the formation and development of CD4+ TRM in the SI. These findings provide insights into the development, differentiation, and persistence of CD4+ TRM in response to viral infection.
SCIENCE IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Remi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Summary: Through studying CD4(+) T cells of HIV-1 patients, the importance of effector memory T cells in the persistence of HIV-1 has been identified, and Nef has been suggested as a potential therapeutic target.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Virology
Steven A. Yukl, Shahzada Khan, Tsui-Hua Chen, Martin Trapecar, Frank Wu, Guorui Xie, Sushama Telwatte, Daniel Fulop, Alexander R. Pico, Gregory M. Laird, Kristen D. Ritter, Norman G. Jones, Chuanyi M. Lu, Robert F. Siliciano, Nadia R. Roan, Jeffrey M. Milush, Ma Somsouk, Steven G. Deeks, Peter W. Hunt, Shomyseh Sanjabi
Summary: This study found that circulating CD103(+) CD4 T cells are enriched for cells in a latent-like state of HIV infection, with a gene expression profile closer to gut CD4 T cells. Some of the genes expressed in these cells are associated with HIV expression and could contribute to latent HIV infection in the gut, suggesting potential new targets for HIV cure therapies.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yashavanth S. Lakshmanappa, Jamin W. Roh, Niharika N. Rane, Ashok R. Dinasarapu, Daphne D. Tran, Vijayakumar Velu, Anandi N. Sheth, Igho Ofotokun, Rama R. Amara, Colleen F. Kelley, Elaine Waetjen, Smita S. Iyer
Summary: The study found that HIV preferentially infects alpha(4)beta(+)(7) CD4 T cells and enriches genes regulating cell cycle progression and cellular metabolism in the blood. Unlike their blood counterparts, rectal alpha(4)beta(+)(7) CD4 T cells exhibit a core tissue-residency gene expression program.
Article
Biology
Marie Strickland, Salanne Lee, Shi Yong Neo, Akhila Balachander, Ivy Low, Seri Mustafah, Wah Ing Goh, Graham D. D. Wright, Anis Larbi, Sylvia L. F. Pender
Summary: The study focuses on investigating the impact of mitochondrial dysfunction on immune responses to infection and vaccination in the elderly population. Specifically, it examines the metabolic responses and mitochondrial dynamics of CD4+ TEMRA cells and other CD4+ memory T cell subtypes. The results show that CD4+ TEMRA cells exhibit altered mitochondrial dynamics, increased glucose uptake, and higher mitochondrial mass, which may contribute to impaired responses to infection and vaccination.
Article
Immunology
Sarah L. Bevington, Remi Fiancette, Dominika W. Gajdasik, Peter Keane, Jake K. Soley, Claire M. Willis, Daniel J. L. Coleman, David R. Withers, Peter N. Cockerill
Summary: Research reveals that T cell immunological memory is established within 7 days post-infection, with epigenetic programs playing a crucial role in Th differentiation and memory T cell formation. Memory T cell-specific regulatory elements contribute to enhanced inducible responses during secondary antigen exposures.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Michael L. Dixon, Jonathan D. Leavenworth, Jianmei W. Leavenworth
Summary: Regulatory T-cells, particularly effector Tregs (eTregs), play a crucial role in maintaining self-tolerance and tissue homeostasis, with potential implications in tumor development. Understanding the mechanisms that modulate the stability and suppressive function of tumoral Tregs, such as eTregs and T-FR cells, can lead to the development of more effective cancer immunotherapies that target the tumor microenvironment while minimizing systemic side effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Xiaofan Yang, Ting Huang, Tiantian Wang, Hongbo Gao, Haitao Zhang, Wen Peng, Jiacong Zhao, Shujing Hu, Panpan Lu, Zhongsi Hong, Bo Li, Kai Deng
Summary: This study demonstrates the critical role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency. Knockout of MAT2A enhances the reactivation of latent HIV-1 by reducing DNA and histone methylation. Plasma SAM levels are positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Marco Kunzli, David Masopust
Summary: This review provides updates on our understanding of the biology of memory CD4(+) T cells as well as key technological advances that facilitate their characterization.
Article
Biochemistry & Molecular Biology
Aurelio Cafaro, Giovanni Barillari, Sonia Moretti, Clelia Palladino, Antonella Tripiciano, Mario Falchi, Orietta Picconi, Maria Rosaria Pavone Cossut, Massimo Campagna, Angela Arancio, Cecilia Sgadari, Claudia Andreini, Lucia Banci, Paolo Monini, Barbara Ensoli
Summary: Previous research has shown that Tat protein of HIV-1 can enter dendritic cells through integrins alpha 5 beta 1, alpha v beta 3, and alpha v beta 5 upon binding of its RGD domain. Endothelial cells exposed to inflammatory cytokines selectively bind and take up Tat, leading to HIV replication. Tat entry is dependent on conformation and energy, and can be blocked by integrin ligands or antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Caroline Dufour, Corentin Richard, Marion Pardons, Marta Massanella, Antoine Ackaoui, Ben Murrell, Bertrand Routy, Rejean Thomas, Jean-Pierre Routy, Remi Fromentin, Nicolas Chomont
Summary: The phenotypic diversity of HIV-infected cells persisting during antiretroviral therapies (ART) was investigated. CD4+ T cells expressing integrin VLA-4 were found to be enriched in replication-competent HIV. Clonally expanded cells with identical proviruses displayed diverse phenotypes, indicating the role of cellular proliferation in the phenotypic diversification of the HIV reservoir. Genetically intact and inducible viral genomes were associated with higher levels of VLA-4 expression in CD4+ T cells. Replication-competent HIV was highly enriched in memory CD4+ T cells expressing high levels of VLA-4.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Trupti Vardam-Kaur, Sarah van Dijk, Changwei Peng, Kelsey M. Wanhainen, Stephen C. Jameson, Henrique Borges da Silva
Summary: This study found that unequal upregulation of P2RX7 in effector CD8+ T cells is a foundational element in the early fate determination of Tcm and Trm cells. P2RX7 negatively regulates the expression of the transcriptional repressor Zeb2, affecting the formation of Tcm and Trm cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Jatin Machhi, Pravin Yeapuri, Yaman Lu, Emma Foster, Rupesh Chikhale, Jonathan Herskovitz, Krista L. Namminga, Katherine E. Olson, Mai Mohamed Abdelmoaty, Ju Gao, Rolen M. Quadros, Tomomi Kiyota, Liang Jingjing, Bhavesh D. Kevadiya, Xinglong Wang, Yutong Liu, Larisa Y. Poluektova, Channabasavaiah B. Gurumurthy, R. Lee Mosley, Howard E. Gendelman
Summary: Alzheimer's disease is characterized by pathological deposition of misfolded self-protein amyloid beta, leading to neuroinflammation. Effector T cells induced by self-antigens accelerate disease progression, suggesting a potential therapeutic target in controlling AD pathology.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Cell Biology
Zilun Li, Meixiu Peng, Pin Chen, Chenshu Liu, Ao Hu, Yixin Zhang, Jiangyun Peng, Jiang Liu, Yihui Li, Wenxue Li, Wei Zhu, Dongxian Guan, Yang Zhang, Hongyin Chen, Jiuzhou Li, Dongxiao Fan, Kan Huang, Fen Lin, Zefeng Zhang, Zeling Guo, Hengli Luo, Xi He, Yuanyuan Zhu, Linghua Li, Bingding Huang, Weikang Cai, Lei Gu, Yutong Lu, Kai Deng, Li Yan, Sifan Chen
Summary: The study indicates that impairment of the ACE2 pathway is a key factor in the metabolic complications caused by COVID-19. Through screening and experiments, the researchers identified imatinib, methazolamide, and harpagoside as compounds that can directly activate ACE2. These compounds can improve metabolic disturbances and inhibit viral entry.
Review
Virology
Yu-Chan Yang, Hung-Chih Yang
Summary: Hepatitis B virus (HBV) infection remains a global public health issue, and the current antiviral therapy fails to cure it. CRISPR-mediated gene editing has emerged as a promising approach for HBV cure, but it faces challenges such as off-target effects and difficulty in finding conserved target sequences.
Article
Cell Biology
Yaochang Yuan, Xiantao Zhang, Ran Chen, Yuzhuang Li, Bolin Wu, Rong Li, Fan Zou, Xiancai Ma, Xuemei Wang, Qier Chen, Jieyi Deng, Yongli Zhang, Tao Chen, Yingtong Lin, Shumei Yan, Xu Zhang, Congrong Li, Xiuqing Bu, Yi Peng, Changwen Ke, Kai Deng, Ting Pan, Xin He, Yiwen Zhang, Hui Zhang
Summary: A bivalent nanoparticle vaccine has been developed to address immune evasion caused by SARS-CoV-2 variants. Through different immunization strategies, this vaccine can induce strong neutralizing antibody response and provide full protection against infection with D614G or B.1.351 strains in mice and rhesus macaques. Furthermore, a booster dose of the bivalent vaccine can elicit cross-neutralizing antibodies against SARS-CoV-2 variants in individuals previously vaccinated with the D614G-specific vaccine.
Article
Gastroenterology & Hepatology
Ting-Yuan Lan, Yen-Chun Lin, Tai-Chung Tseng, Hung-Chih Yang, Jui-Hung Kao, Chiao-Feng Cheng, Tai-Ju Lee, Shang-Chin Huang, Cheng-Hsun Lu, Ko-Jen Li, Song -Chou Hsieh
Summary: In HBsAg-negative patients receiving rituximab for autoimmune diseases, the risk of HBV reactivation may exist. Older age, positive HBc antibody, undetectable hepatitis B surface antibody level at initiation, and higher rituximab dose may be associated with a higher risk of HBV reactivation.
Article
Medicine, General & Internal
Wang-Huei Sheng, Si-Man Ieong, Pin-Hung Lin, Ming-Ju Hsieh, Hung-Chih Yang, Ching-Fu Pan, Tai-Ling Chao, Sui-Yuan Chang, Shan-Chwen Chang
Summary: The study investigated the immunogenicity and adverse events of the third dose of mRNA vaccines in healthy adults. The results showed that the third dose mRNA COVID-19 vaccines markedly enhanced cellular and humoral responses and were safe. Immunological responses and adverse events were higher in individuals receiving the full-dose mRNA-1273 vaccine compared to other groups.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2023)
Article
Biochemistry & Molecular Biology
Kolin M. Clark, Josh G. Kim, Qiankun Wang, Hongbo Gao, Rachel M. Presti, Liang Shan
Summary: The sensitization of the CARD8 inflammasome to non-nucleoside reverse transcriptase inhibitors (NNRTIs) can be achieved through chemical inhibition of the negative regulator DPP9. The DPP9 inhibitor Val-boroPro (VbP) can kill HIV-1-infected cells without NNRTIs and synergize with NNRTIs to promote clearance of infected cells. This offers a promising strategy for enhancing NNRTI efficacy in eliminating HIV-1 reservoirs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Oncology
Chian-Tzu Huang, Yu-Long Chu, Tung-Hung Su, Shang-Chin Huang, Tai-Chung Tseng, Shih-Jer Hsu, Sih-Han Liao, Chun-Ming Hong, Chen-Hua Liu, Hung-Chih Yang, Chun-Jen Liu, Pei-Jer Chen, Jia-Horng Kao
Summary: This study aimed to identify candidates for surgical resection (SR) in Barcelona Clinic Liver Cancer (BCLC) -A/B HCC beyond the Milan criteria with survival benefit. The study found that patients with tumor burden beyond the up-to-7 criteria but within 3 tumors had better overall survival (OS) with SR compared to transarterial chemoembolization (TACE), suggesting that SR should be considered in resectable patients.
Letter
Surgery
Mary G. Bowring, Jessica M. Ruck, Mitchell G. Bryski, William Werbel, Aaron A. R. Tobian, Allan B. Massie, Dorry L. Segev, Christine M. Durand
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Microbiology
Ting Huang, Jinfeng Cai, Peipei Wang, Jiasheng Zhou, Haitao Zhang, Ziqi Wu, Jiacong Zhao, Zhanlian Huang, Kai Deng
Summary: Although ART can effectively suppress viral replication, it cannot cure HIV-1 infection due to viral latent reservoir. Block and lock strategy aims to silence viral reservoir and prevent viral rebound. Ponatinib, an FDA-approved drug, can repress HIV-1 reactivation and does not cause cytotoxicity or cell dysfunction. It inhibits proviral HIV-1 transcription by blocking the AKT-mTOR pathway.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Immunology
Nitipong Permpalung, Teresa Po-Yu Chiang, Robin K. Avery, Darin Ostrander, Kausik Datta, Dorry L. Segev, Christine M. Durand, Sean X. Zhang, Allan B. Massie, Kieren A. Marr
Summary: A retrospective study was conducted to investigate COVID-19-associated pulmonary aspergillosis (CAPA), which is likely underdiagnosed and lacks sensitive diagnostic tools. A CAPA prediction model was built using multivariable logistic regression analysis, and the performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). The model identified several factors, such as age, intubation time, dexamethasone treatment, and underlying diseases, that were significantly associated with CAPA, resulting in an AUC of 0.75. Screening at a cutoff of =0.085, the model showed a sensitivity of 82%, specificity of 51%, positive predictive value of 18.6%, and negative predictive value of 95.3%.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Medicine, Research & Experimental
Yuhao Li, Hongbo Gao, Kolin M. Clark, Liang Shan
Summary: HIV-1 primarily uses CCR5 as its coreceptor but can occasionally switch to a CXCR4-tropic virus during late-stage infection. CCR5+CD4+ T cells, which are abundant in viremic individuals and SIV-infected nonhuman primates, play a major role in virus production. The differentiation and survival of CCR5+CD4+ T cells are regulated by IL-15, suggesting potential implications for HIV-1 infection and the boosting of anti-HIV-1 immunity.
Review
Infectious Diseases
Grace Chung-Yan Lui, Grace Lai-Hung Wong, Hung-Chih Yang, Wang-Huei Sheng, Sun Hee Lee
Summary: This article describes the prevalence, clinical practice, and management recommendations for people living with HIV-HBV co-infection in Asia. The study found that the prevalence of HIV and HBV co-infection is higher in Asia and varies significantly between different regions. Early screening and treatment are important in preventing complications. Additionally, HBV vaccination programs are effective in reducing co-infection rates.
Article
Cardiac & Cardiovascular Systems
Nitipong Permpalung, Tao Liang, Shilpa Gopinath, Katrina Bazemore, Joby Mathew, Darin Ostrander, Christine M. Durand, Shmuel Shoham, Sean X. Zhang, Kieren A. Marr, Robin K. Avery, Pali D. Shah
Summary: This study found that respiratory viral infections are associated with chronic lung allograft dysfunction and mortality in lung transplant recipients. Secondary invasive fungal infections were also found to be prevalent in these patients and were associated with CLAD progression/death. Screening for fungal infections is crucial in this setting.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Letter
Medicine, General & Internal
Niraj M. Desai, Sherry G. Leung, Jennifer D. Motter, Dorry L. Segev, Daniel Warren, Christine M. Durand
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Xiaofei Wang, Ao Hu, Xiangyu Chen, Yixin Zhang, Fei Yu, Shuai Yue, Arong Li, Junsong Zhang, Zhiwei Pan, Yang Yang, Yao Lin, Leiqiong Gao, Jing Zhou, Jing Zhao, Fang Li, Yaling Shi, Feng Huang, Xiaofan Yang, Yi Peng, Luoyang Tu, Huan Zhang, Huanying Zheng, Jun He, Hui Zhang, Lifan Xu, Qizhao Huang, Yongqun Zhu, Kai Deng, Lilin Ye
Summary: This study demonstrates an antibody that efficiently neutralizes both SARS-CoV-2 and its variants, providing insights for the development of universal vaccines.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)