Medicine and Health Sciences Commons^™

Sars-Cov-2 Omicron Ba.1 Variant Infection Of Human Colon Epithelial Cells, Avan Antia, David M Alvarado, Qiru Zeng, Luis A Casorla-Perez, Deanna L Davis, Naomi M Sonnek, Matthew A Ciorba, Siyuan Ding

2020-Current year OA Pubs

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed …

Antiviral Cellular Therapy For Enhancing T-Cell Reconstitution Before Or After Hematopoietic Stem Cell Transplantation (Aces): A Two-Arm, Open Label Phase Ii Interventional Trial Of Pediatric Patients With Risk Factor Assessment, Michael D Keller, Jeffrey J Bednarski, Et Al.

2020-Current year OA Pubs

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST …

Estimated Health Benefits, Costs And Cost-Effectiveness Of Eliminating Industrial Trans-Fatty Acids In Nigeria: Cost-Effectiveness Analysis, Matti Marklund, Leopold N Aminde, Mary Njeri Wanjau, Boni M Ale, Adedayo E Ojo, Clementina E Okoro, Abimbola Adegboye, Liping Huang, J Lennert Veerman, Jason Hy Wu, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

INTRODUCTION: Nigeria is committed to reducing industrial

METHODS: The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and

RESULTS: Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 …

Encoding Of Visual Objects In The Human Medial Temporal Lobe, Yue Wang, Runnan Cao, Shuo Wang

2020-Current year OA Pubs

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our …

Characterization Of Early Markers Of Disease In The Mouse Model Of Mucopolysaccharidosis Iiib, Katherine B Mccullough, Amanda Titus, Kate Reardon, Sara Conyers, Joseph D Dougherty, Xia Ge, Joel R Garbow, Patricia Dickson, Carla M Yuede, Susan E Maloney

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in …

The Brain Gene Registry: A Data Snapshot, Dustin Baldridge, Levi Kaster, Catherine Sancimino, Siddharth Srivastava, Sophie Molholm, Aditi Gupta, Inez Oh, Virginia Lanzotti, Daleep Grewal, Erin Rooney Riggs, Juliann M Savatt, Rachel Hauck, Abigail Sveden, Brain Gene Registry Consortium, John N Constantino, Joseph Piven, Christina A Gurnett, Maya Chopra, Heather Hazlett, Philip R O Payne

2020-Current year OA Pubs

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment …

Cellular Geometry And Epithelial-Mesenchymal Plasticity Intersect With Piezo1 In Breast Cancer Cells, Choon Leng So, Mélanie Robitaille, Francisco Sadras, Michael H Mccullough, Michael J G Milevskiy, Geoffrey J Goodhill, Sarah J Roberts-Thomson, Gregory R Monteith

2020-Current year OA Pubs

Differences in shape can be a distinguishing feature between different cell types, but the shape of a cell can also be dynamic. Changes in cell shape are critical when cancer cells escape from the primary tumor and undergo major morphological changes that allow them to squeeze between endothelial cells, enter the vasculature, and metastasize to other areas of the body. A shift from rounded to spindly cellular geometry is a consequence of epithelial-mesenchymal plasticity, which is also associated with changes in gene expression, increased invasiveness, and therapeutic resistance. However, the consequences and functional impacts of cell shape changes and the …

Topmed Imputed Genomics Enhances Genomic Atlas Of The Human Proteome In Brain, Cerebrospinal Fluid, And Plasma, Heng Yi, Qijun Yang, Charlie Repaci, Cheolmin Matthew Lee, Gyujin Heo, Jigyasha Timsina, Priyanka Gorijala, Chengran Yang, John Budde, Lihua Wang, Carlos Cruchaga, Yun Ju Sung

2020-Current year OA Pubs

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated …

Novel Jak Inhibitors To Reduce Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation In A Preclinical Mouse Model, Sena Kim, Peter Ruminski, Megh Singh, Karl Staser, Kidist Ashami, Julie Ritchey, Sora Lim, John F Dipersio, Jaebok Choi

2020-Current year OA Pubs

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies. We previously demonstrated that targeting JAK1/JAK2, mediators of interferon-gamma receptor (IFNGR) and IL-6 receptor signaling, in donor T cells using baricitinib and ruxolitinib results in a significant reduction in GvHD after allo-HCT. Furthermore, we showed that balanced …

Recruitment Strategies In The Integration Of Mobile Health Into Sickle Cell Disease Care To Increase Hydroxyurea Utilization Study (Mesh): Multicenter Survey Study, Chinonyelum Nwosu, Hamda Khan, Rita Masese, Judith M Nocek, Siera Gollan, Taniya Varughese, Sarah Bourne, Cindy Clesca, Sara R Jacobs, Ana Baumann, Lisa M Klesges, Nirmish Shah, Jane S Hankins, Matthew P Smeltzer

2020-Current year OA Pubs

BACKGROUND: Hydroxyurea is an evidence-based disease-modifying therapy for sickle cell disease (SCD) but is underutilized. The Integration of Mobile Health into Sickle Cell Disease Care to Increase Hydroxyurea Utilization (meSH) multicenter study leveraged mHealth to deliver targeted interventions to patients and providers. SCD studies often underenroll; and recruitment strategies in the SCD population are not widely studied. Unanticipated events can negatively impact enrollment, making it important to study strategies that ensure adequate study accrual.

OBJECTIVE: The goal of this study was to evaluate enrollment barriers and the impact of modified recruitment strategies among patients and providers in the meSH study …

Host Response During Unresolved Urinary Tract Infection Alters Female Mammary Tissue Homeostasis Through Collagen Deposition And Timp1, Samantha Henry, Xue-Yan He, Et Al.

2020-Current year OA Pubs

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad …

Brief Report: Substance Use Care Continuum In Women With And Without Hiv In The Southern United States, Aditi Ramakrishnan, Ayako W. Fujita, C. Christina Mehta, Tracey E. Wilson, Steve Shoptaw, Adam Carrico, Adaora A. Adimora, Ellen F. Eaton, Deborah L. Jones, Aruna Chandran, Anandi N. Sheth

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor outcomes among persons living with HIV. Women living with HIV (WWH) in the United States are disproportionately affected in the South, and examining SU patterns, treatment, and HIV outcomes in this population is integral to addressing HIV and SU disparities.

METHODS: WWH and comparable women without HIV (WWOH) who enrolled 2013-2015 in the Women's Interagency HIV Study Southern sites (Atlanta, Birmingham/Jackson, Chapel Hill, and Miami) and reported SU (self-reported nonmedical use of drugs) in the past year were included. SU and treatment were described annually from enrollment to the end of follow-up. HIV …

Clinical Implications Of Inaccurate Potassium Determination In Hemolyzed Pediatric Blood Specimens, Dennis J Dietzen, Ronald Jackups, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Analysis of whole blood specimens is rapid and saves blood, but hemolysis may go undetected and compromise the accuracy of potassium measurement. We aimed to define the frequency and magnitude of error in whole blood potassium measurement.

METHODS: 34 months of whole blood and plasma potassium data were extracted from patients aged less than 2 years at the time of sample acquisition. Hemolysis was detected using the plasma "H index." The magnitude of potassium bias was estimated from the difference between paired whole blood and plasma measurement separated by less than 2 h.

RESULTS: 56,000 of the 105,000 data …

Treating Sex And Gender Differences As A Continuous Variable Can Improve Precision Cancer Treatments, Wei Yang, Joshua B Rubin

2020-Current year OA Pubs

BACKGROUND: The significant sex and gender differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. One barrier to translation is that cancer phenotypes cannot be segregated into distinct male versus female categories. Instead, within this convenient but contrived dichotomy, male and female cancer phenotypes are highly overlapping and vary between female- and male- skewed extremes. Thus, sex and gender-specific treatments are unrealistic, and our translational goal should be adaptation of treatment to the variable effects of sex and gender on targetable pathways.

METHODS: To overcome this obstacle, we profiled the similarities in 8370 transcriptomes …

Evolution Of The Transforaminal Lumbar Interbody Fusion (Tlif): From Open To Percutaneous To Patient-Specific, Peter N Drossopoulos, Favour C Ononogbu-Uche, Troy Q Tabarestani, Chuan-Ching Huang, Mounica Paturu, Anas Bardeesi, Wilson Z Ray, Christopher I Shaffrey, C Rory Goodwin, Melissa Erickson, John H Chi, Muhammad M Abd-El-Barr

2020-Current year OA Pubs

The transforaminal lumbar interbody fusion (TLIF) has seen significant evolution since its early inception, reflecting advancements in surgical techniques, patient safety, and outcomes. Originally described as an improvement over the posterior lumbar interbody fusion (PLIF), the TLIF began as an open surgical procedure, that notably reduced the need for the extensive neural retractation that hindered the PLIF. In line with the broader practice of surgery, trending toward minimally invasive access, the TLIF was followed by the development of the minimally invasive TLIF (MIS-TLIF), a technique that further decreased tissue trauma and postoperative complications. Subsequent advancements, including Trans-Kambin's Triangle TLIF (percLIF) …

"In Our Community, We Normalize Pain": Discussions Around Menstruation And Uterine Fibroids With Black Women And Latinas, Minerva Orellana, Karen N Dsouza, Jane Q Yap, Abhirami Sriganeshan, M Elena Jones, Charis Johnson, Megan Allyse, Sateria Venable, Elizabeth A Stewart, Felicity Enders, Joyce E Balls-Berry

2020-Current year OA Pubs

BACKGROUND: Uterine fibroids are non-cancerous neoplasms that arise from the uterus affecting over 75% of women. However, there is a disparity with Black women having an increased prevalence of nearly 80%. Black women also experience increased symptom burden, including younger age at the time of diagnosis and increased number and volume of fibroids. Less is known about other ethnoracially diverse women such as Latinas and the potential cultural impacts on fibroid burden and treatment.

METHODS: Community engagement studios were conducted to facilitate discussions with stakeholders on their uterine fibroid and menstruation experience. We recruited Black women (n = 6) diagnosed …

Mastigoneme Structure Reveals Insights Into The O-Linked Glycosylation Code Of Native Hydroxyproline-Rich Helices, Jin Dai, Meisheng Ma, Qingwei Niu, Robyn J Eisert, Xiangli Wang, Poulomi Das, Karl F Lechtreck, Susan K Dutcher, Rui Zhang, Alan Brown

2020-Current year OA Pubs

Hydroxyproline-rich glycoproteins (HRGPs) are a ubiquitous class of protein in the extracellular matrices and cell walls of plants and algae, yet little is known of their native structures or interactions. Here, we used electron cryomicroscopy (cryo-EM) to determine the structure of the hydroxyproline-rich mastigoneme, an extracellular filament isolated from the cilia of the alga Chlamydomonas reinhardtii. The structure demonstrates that mastigonemes are formed from two HRGPs (a filament of MST1 wrapped around a single copy of MST3) that both have hyperglycosylated poly(hydroxyproline) helices. Within the helices, O-linked glycosylation of the hydroxyproline residues and O-galactosylation of interspersed serine residues create a …

Use Of Barium For Diagnosis Of Colonic Perforation Leads To Challenging Barium Peritonitis, Ariana Naaseh, Jorge G Zarate Rodriguez, Matthew J Mchale, Grace M Niziolek, Thoi H Ngo, John P Kirby, Lindsay M Kranker

2020-Current year OA Pubs

No abstract provided.

Macromolecular Condensation Organizes Nucleolar Sub-Phases To Set Up A Ph Gradient, Matthew R King, Kiersten M Ruff, Andrew Z Lin, Avnika Pant, Mina Farag, Jared M Lalmansingh, Tingting Wu, Martin J Fossat, Wei Ouyang, Matthew D Lew, Emma Lundberg, Michael D Vahey, Rohit V Pappu

2020-Current year OA Pubs

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this …

Organizing The Dissemination And Implementation Field: Who Are We, What Are We Doing, And How Should We Do It?, Gretchen J R Buchanan, Lindsey M Filiatreau, Julia E Moore

2020-Current year OA Pubs

Two decades into its tenure as a field, dissemination and implementation (D&I) scientists have begun a process of self-reflection, illuminating a missed opportunity to bridge the gap between research and practice-one of the field's foundational objectives. In this paper, we, the authors, assert the research-to-practice gap has persisted, in part due to an inadequate characterization of roles, functions, and processes within D&I. We aim to address this issue, and the rising tension between D&I researchers and practitioners, by proposing a community-centered path forward that is grounded in equity.We identify key players within the field and characterize their unique roles using …

Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele

2020-Current year OA Pubs

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, …

Impact Of Self-Reported Loss Of Balance And Gait Disturbance On Outcomes Following Adult Spinal Deformity Surgery, Bassel G Diebo, Munish C Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.

Pathophysiology Of Chikungunya Virus Infection Associated With Fatal Outcomes, William M De Souza, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage …

Bone Canonical Wnt Signaling Is Downregulated In Type 2 Diabetes And Associates With Higher Advanced Glycation End-Products (Ages) Content And Reduced Bone Strength, Giulia Leanza, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Nicola Napoli, Et Al.

2020-Current year OA Pubs

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, And Death: United States, 2022-2023, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain.

METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by …

Lung Type 3 Innate Lymphoid Cells Respond Early Following Mycobacterium Tuberculosis Infection, Shibali Das, Kuldeep Singh Chauhan, Mushtaq Ahmed, Sadia Akter, Lan Lu, Marco Colonna, Shabaana A Khader

2020-Current year OA Pubs

UNLABELLED: Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during

IMPORTANCE: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during

Mechanism Of Antagonist Ligand Binding To Rev-Erbα, Mohammad Homaidur Rahman, Lamees Hegazy

2020-Current year OA Pubs

REV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also …

Transcription Factor C/Ebpα Is Required For The Development Of Ly6chi Monocytes But Not Ly6clo Monocytes, Sunkyung Kim, Jing Chen, Feiya Ou, Tian-Tian Liu, Suin Jo, William E Gillanders, Theresa L Murphy, Kenneth M Murphy

2020-Current year OA Pubs

Monocytes comprise two major subsets, Ly6C

Parenting Practices And Interventions During The Covid-19 Pandemic Lockdown: An Exploratory Cross-Sectional Study Of Caregivers In Brazil, Mexico, And The United States, Mariana M Juras, Acileide Cristiane F Coelho, Alejandro L Vázquez, Michela Ribeiro, Marina Kohlsdorf, Alice Lima Custódio, Nancy G Amador Buenabad, Lucia Vazquez Perez, Cole Hooley, Miya L Barnett, Ana A Baumann

2020-Current year OA Pubs

INTRODUCTION: The COVID-19 pandemic led countries' governments to rapidly establish lockdowns and social distancing, which altered family routines and the quality of family relationships worldwide.

OBJECTIVES: This exploratory cross-sectional study aimed to identify the impacts of the social distancing and lockdown in parenting practices of caregivers from Brazil, Mexico, and the USA, and to analyze the continuity of parenting intervention support for children and their families at the beginning of the pandemic in these countries.

METHODS: The sample consisted of 704 caregivers of children (286 from Brazil, 225 from Mexico, and 193 from the USA) who answered an online survey …

A Macrophage-Cell Model Of Hiv Latency Reveals The Unusual Importance Of The Bromodomain Axis, Javan K Kisaka, Daniel Rauch, Malachi Griffith, George B Kyei

2020-Current year OA Pubs

BACKGROUND: Although macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells.

METHODS: We created single-cell clones of THP-1 cells infected with a single …