ARL15, a GTPase implicated in rheumatoid arthritis, potentially repositions its truncated N-terminus as a function of guanine nucleotide binding.

The ADP ribosylation factor like protein 15 (ARL15) gene encodes for an uncharacterized GTPase associated with rheumatoid arthritis (RA) and other metabolic disorders. Investigation of the structural and functional attributes of ARL15 is important to position the protein as a potential drug target. Using spectroscopy, we demonstrated that ARL15 exhibits properties inherent of GTPases. The Km and Vmax of the enzyme were calculated to be 100 µM and 1.47 µmole/min/µL, respectively. The equilibrium dissociation constant (Kd) of GTP binding with ARL15 was estimated to be about eight-fold higher than that of GDP. Small Angle X-ray Scattering (SAXS) data indicated that in solution, the apo state of monomeric ARL15 adopts a shape characterized by a globe of maximum linear dimension (Dmax) of 6.1 nm, and upon binding to GTP or GDP, the vector distribution profile changes to peak-n-tail shoulder with Dmax extended to 7.6 and 7.7 nm, respectively. Structure restoration using a sequence-based template and experimental SAXS data provided the first visual insight revealing that the folded N-terminal in the unbound state of the protein may toggle open upon binding to guanine nucleotides. The conformational dynamics observed in the N-terminal region offer a scope to develop drugs that target this unique GTPase, potentially providing treatments for a range of metabolic disorders.

Boswellic Acids: A Critical Appraisal of Their Therapeutic and Nutritional Benefits in Chronic Inflammatory Diseases.

BACKGROUND: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases. OBJECTIVE: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species. METHODS: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases. RESULT: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects. CONCLUSION: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in.

ARL15 and its Multiple Disease Association: Emerging Functions and Potential Therapeutic Application.

ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.

Recent Patents on Solid Dispersions Emphasize Promising Benefits in Solubility Enhancement of Poorly Water-soluble Drugs.

BACKGROUND: In the development of drug delivery systems, drugs' solubility remains the most challenging constraint. Many newly synthesized chemical compounds are available, but they involve low solubility and poor permeability restrictions. Among various drug delivery systems, the utilization of solid dispersion technologies has become more focused due to their promising benefits. OBJECTIVE: This technology has attracted extensive attention for dissolution rate improvement along with substantial bioavailability enhancement of poorly water-soluble drug candidates. METHODS: Many approaches have been employed for preparing solid dispersions, such as the melting method, hot melt extrusion, solvent evaporation process, fusion and kneading method, spray drying technique, co-grinding and freeze drying, supercritical fluid technology, etc. Result: A wide variety of hydrophilic and hydrophobic materials are available as carriers, which are employed in the formulation of solid dispersions. Depending on the carrier characteristics, immediate- release solid dispersions and/or controlled-release solid dispersions can be formulated. Multiple hydrophilic materials have been explored for heightening dissolution features with enhanced bioavailability of poorly water-soluble drug molecules. The availability of commercially available products further validates the utility of solid dispersion technology in drug delivery systems. CONCLUSION: In the current manuscript, an attempt has been made to highlight the comprehensive development techniques, characterization techniques, recent solid dispersion technologies, clinical trial studies, and patented technology, along with studies heightening the dissolution behavior of numerous poorly aqueous soluble drugs. The major stability issues affecting the suitability of solid dispersions are also discussed.

In silico analysis of angiotensin-converting enzyme inhibitory compounds obtained from soybean [Glycine max (L.) Merr.].

Cardiovascular diseases (CVDs) are one of the major reasons for deaths globally. The renin-angiotensin-aldosterone system (RAAS) regulates body hypertension and fluid balance which causes CVD. Angiotensin-converting enzyme I (ACE I) is the central Zn-metallopeptidase component of the RAAS playing a crucial role in maintaining homeostasis of the cardiovascular system. The available drugs to treat CVD have many side effects, and thus, there is a need to explore phytocompounds and peptides to be utilized as alternative therapies. Soybean is a unique legume cum oilseed crop with an enriched source of proteins. Soybean extracts serve as a primary ingredient in many drug formulations against diabetes, obesity, and spinal cord-related disorders. Soy proteins and their products act against ACE I which may provide a new scope for the identification of potential scaffolds that can help in the design of safer and natural cardiovascular therapies. In this study, the molecular basis for selective inhibition of 34 soy phytomolecules (especially of beta-sitosterol, soyasaponin I, soyasaponin II, soyasaponin II methyl ester, dehydrosoyasaponin I, and phytic acid) was evaluated using in silico molecular docking approaches and dynamic simulations. Our results indicate that amongst the compounds, beta-sitosterol exhibited a potential inhibitory action against ACE I.

Circulating MicroRNAs: Diagnostic Value as Biomarkers in the Detection of Non-alcoholic Fatty Liver Diseases and Hepatocellular Carcinoma.

Non-alcoholic fatty liver disease (NAFLD), a metabolic-related disorder, is the most common cause of chronic liver disease which, if left untreated, can progress from simple steatosis to advanced fibrosis and eventually cirrhosis or hepatocellular carcinoma, which is the leading cause of hepatic damage globally. Currently available diagnostic modalities for NAFLD and hepatocellular carcinoma are mostly invasive and of limited precision. A liver biopsy is the most widely used diagnostic tool for hepatic disease. But due to its invasive procedure, it is not practicable for mass screening. Thus, noninvasive biomarkers are needed to diagnose NAFLD and HCC, monitor disease progression, and determine treatment response. Various studies indicated that serum miRNAs could serve as noninvasive biomarkers for both NAFLD and HCC diagnosis because of their association with different histological features of the disease. Although microRNAs are promising and clinically useful biomarkers for hepatic diseases, larger standardization procedures and studies are still required.

Tailoring crops with superior product quality through genome editing: an update.

MAIN CONCLUSION: In this review, using genome editing, the quality trait alterations in important crops have been discussed, along with the challenges encountered to maintain the crop products' quality. The delivery of economic produce with superior quality is as important as high yield since it dictates consumer's acceptance and end use. Improving product quality of various agricultural and horticultural crops is one of the important targets of plant breeders across the globe. Significant achievements have been made in various crops using conventional plant breeding approaches, albeit, at a slower rate. To keep pace with ever-changing consumer tastes and preferences and industry demands, such efforts must be supplemented with biotechnological tools. Fortunately, many of the quality attributes are resultant of well-understood biochemical pathways with characterized genes encoding enzymes at each step. Targeted mutagenesis and transgene transfer have been instrumental in bringing out desired qualitative changes in crops but have suffered from various pitfalls. Genome editing, a technique for methodical and site-specific modification of genes, has revolutionized trait manipulation. With the evolution of versatile and cost effective CRISPR/Cas9 system, genome editing has gained significant traction and is being applied in several crops. The availability of whole genome sequences with the advent of next generation sequencing (NGS) technologies further enhanced the precision of these techniques. CRISPR/Cas9 system has also been utilized for desirable modifications in quality attributes of various crops such as rice, wheat, maize, barley, potato, tomato, etc. The present review summarizes salient findings and achievements of application of genome editing for improving product quality in various crops coupled with pointers for future research endeavors.

VGGIN-Net: Deep Transfer Network for Imbalanced Breast Cancer Dataset.

In this paper, we have presented a novel deep neural network architecture involving transfer learning approach, formed by freezing and concatenating all the layers till block4 pool layer of VGG16 pre-trained model (at the lower level) with the layers of a randomly initialized naïve Inception block module (at the higher level). Further, we have added the batch normalization, flatten, dropout and dense layers in the proposed architecture. Our transfer network, called VGGIN-Net, facilitates the transfer of domain knowledge from the larger ImageNet object dataset to the smaller imbalanced breast cancer dataset. To improve the performance of the proposed model, regularization was used in the form of dropout and data augmentation. A detailed block-wise fine tuning has been conducted on the proposed deep transfer network for images of different magnification factors. The results of extensive experiments indicate a significant improvement of classification performance after the application of fine-tuning. The proposed deep learning architecture with transfer learning and fine-tuning yields the highest accuracies in comparison to other state-of-the-art approaches for the classification of BreakHis breast cancer dataset. The articulated architecture is designed in a way that it can be effectively transfer learned on other breast cancer datasets.

Diabetic retinopathy screening using deep learning for multi-class imbalanced datasets.

Screening and diagnosis of diabetic retinopathy disease is a well known problem in the biomedical domain. The use of medical imagery from a patient's eye for detecting the damage caused to blood vessels is a part of the computer-aided diagnosis that has immensely progressed over the past few years due to the advent and success of deep learning. The challenges related to imbalanced datasets, inconsistent annotations, less number of sample images and inappropriate performance evaluation metrics has caused an adverse impact on the performance of the deep learning models. In order to tackle the effect caused by class imbalance, we have done extensive comparative analysis between various state-of-the-art methods on three benchmark datasets of diabetic retinopathy: - Kaggle DR detection, IDRiD and DDR, for classification, object detection and segmentation tasks. This research could serve as a concrete baseline for future research in this field to find appropriate approaches and deep learning architectures for imbalanced datasets.

Time-Restricted Eating Regimen Differentially Affects Circulatory miRNA Expression in Older Overweight Adults.

Time-restricted eating (TRE), a popular form of intermittent fasting, has been demonstrated to provide multiple health benefits, including an extension of healthy lifespan in preclinical models. While the specific mechanisms remain elusive, emerging research indicates that one plausible mechanism through which TRE may confer health benefits is by influencing the expression of the epigenetic modulator circulatory miRNAs, which serve as intercellular communicators and are dysregulated in metabolic disorders, such as obesity. Therefore, the goal of this pilot study is to examine the effects of a 4-week TRE regimen on global circulatory miRNA from older (≥65 years) overweight participants. Pre- and post-TRE regimen serum samples from nine individuals who participated in the Time to Eat clinical trial (NCT03590847) and had a significant weight loss (2.6 kg, p < 0.01) were analyzed. The expressions of 2083 human miRNAs were quantified using HTG molecular whole transcriptome miRNA assay. In silico analyses were performed to determine the target genes and biological pathways associated with differentially expressed miRNAs to predict the metabolic effects of the TRE regimen. Fourteen miRNAs were differentially expressed pre- and post-TRE regimen. Specifically, downregulated miRNA targets suggested increased expression of transcripts, including PTEN, TSC1, and ULK1, and were related to cell growth and survival. Furthermore, the targets of downregulated miRNAs were associated with Ras signaling (cell growth and proliferation), mTOR signaling (cell growth and protein synthesis), insulin signaling (glucose uptake), and autophagy (cellular homeostasis and survival). In conclusion, the TRE regimen downregulated miRNA, which, in turn, could inhibit the pathways of cell growth and activate the pathways of cell survival and might promote healthy aging. Future mechanistic studies are required to understand the functional role of the miRNAs reported in this study.

Repurposing the Pathogen Box compounds for identification of potent anti-malarials against blood stages of Plasmodium falciparum with PfUCHL3 inhibitory activity.

Malaria has endured as a global epidemic since ages and its eradication poses an immense challenge due to the complex life cycle of the causative pathogen and its tolerance to a myriad of therapeutics. PfUCHL3, a member of the ubiquitin C-terminal hydrolase (UCH) family of deubiquitinases (DUBs) is cardinal for parasite survival and emerges as a promising therapeutic target. In this quest, we employed a combination of computational and experimental approaches to identify PfUCHL3 inhibitors as novel anti-malarials. The Pathogen Box library was screened against the crystal structure of PfUCHL3 (PDB ID: 2WE6) and its human ortholog (PDB ID: 1XD3). Fifty molecules with better comparative score, bioavailability and druglikeliness were subjected to in-vitro enzyme inhibition assay and among them only two compounds effectively inhibited PfUCHL3 activity at micro molar concentrations. Both MMV676603 and MMV688704 exhibited anti-plasmodial activity by altering the parasite phenotype at late stages of the asexual life cycle and inducing the accumulation of polyubiquitinated substrates. In addition, both the compounds were non-toxic and portrayed high selectivity window for the parasite over mammalian cells. This is the first comprehensive study to demonstrate the anti-malarial efficacy of PfUCHL3 inhibitors and opens new avenues to exploit UCH family of DUBs as a promising target for the development of next generation anti-malaria therapy.

Clinical Efficacy of Remdesivir and Favipiravir in the Treatment of COVID-19 Patients: Scenario so far.

The novel SARS-CoV-2 is a new disease that has caused severe destruction to human lives across the globe, including infection, mortality and financial crises, for which, scientific researchers have been directed towards the development of treatment and controlling measures against coronavirus. Currently, there has been no approved drug for the treatment of the disease, but several antiviral drugs have shown therapeutic effects from which, remdesivir and favipiravir are two such drugs. These drugs have shown some therapeutic potential in the treatment of COVID-19 by inhibiting viral enzyme RNA-dependent RNA polymerase. The purpose of this systematic review is to provide an overview of the effectiveness of these two drugs based on the clinical trials reported in current published data.

Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.

Computational insight into the three-dimensional structure of ADP ribosylation factor like protein 15, a novel susceptibility gene for rheumatoid arthritis.

The ARL15 gene (ADP ribosylation factor like protein 15) encodes for an uncharacterized small GTP-binding protein. Its exact role in human physiology remains unknown, but a number of genetic association studies have recognised different variants in this gene to be statistically associated with numerous traits and complex diseases. We have previously reported a novel association of ARL15 with rheumatoid arthritis (RA) based on a genome-wide association study in a north Indian cohort. Subsequent investigations have provided leads for its involvement in RA pathophysiology, especially its potential as a novel therapeutic target. However, the absence of an experimentally determined tertiary structure for ARL15 significantly hinders the understanding of its biochemical and physiological functions, as well as development of potential lead molecules. We, therefore, aimed to derive a high quality, refined model of the three dimensional structure of human ARL15 protein using two different computational protein structure prediction methods - template-based threading and ab initio modelling. The best model each from among the five each derived from both the approaches was selected based on stringent quality assessment and refinement. Molecular dynamics simulations over long timescales revealed the ab initio model to be relatively more stable, and it marginally outperformed the template-based model in the quality assessment as well. A putative GTP-binding site was also predicted using homology for the ARL15 protein, where potential competitive inhibitors can be targeted. This high quality predicted model may provide insights to the biological role(s) of ARL15 and inform and guide further experimental, structural and biochemical characterization efforts.Communicated by Ramaswamy H. Sarma.

Therapeutic enzymes as non-conventional targets in cardiovascular impairments: A comprehensive review.

Over the last few decades, substantial progress has been made towards the understanding of cardiovascular diseases. In-depth mechanistic insights have also provided opportunities to explore novel therapeutic targets and to discover new treatment regimens. Therapeutic enzymes are examples of such opportunities. The enzymes protect against a variety of cardiovascular diseases, however, even minor malfunctioning of these enzymes may lead to deleterious outcomes. Owing to their great versatility, the inhibition and activation of these enzymes are key regulatory approaches to counter the onset and progression of several cardiovascular impairments. While cardiovascular remedies are already available in excess and are efficacious, a comprehensive description of novel therapeutic enzymes to combat cardiovascular diseases would still be of great benefit. In the light of this, the regulation of functional activities of these enzymes also opens a new avenue for the treatment approaches to be employed. This review describes the importance of non-conventional enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), phosphodiesterase (PDE), arginase, superoxide dismutase (SOD), thioredoxin reductase (TXNRD) and selenoprotein T (SELENOT), cytochrome b5 reductase 3 (CYB5R3), epoxide hydrolase (EHs), xanthine oxidoreductase (XOR), matrix metalloprotease (MMPs), and dopamine beta hydroxylase (DBH), as potential candidates in several cardiovascular disorders while highlighting some of the recently targeted therapeutic enzymes in cardiovascular diseases. We also discuss the role of intrinsic antioxidant defense system involved in cardioprotection followed by addressing some of the clinical investigations considering the use of antioxidant as a preferred therapy of cardiovascular complications.

Identification of quantitative trait loci (QTLs) and candidate genes for seed shape and 100-seed weight in soybean [Glycine max (L.) Merr.].

Seed size and shape are important traits determining yield and quality in soybean. Seed size and shape are also desirable for specialty soy foods like tofu, natto, miso, and edamame. In order to find stable quantitative trait loci (QTLs) and candidate genes for seed shape and 100-seed weight, the current study used vegetable type and seed soybean-derived F2 and F2:3 mapping populations. A total of 42 QTLs were mapped, which were dispersed across 13 chromosomes. Of these, seven were determined to be stable QTLs and five of them were major QTLs, namely qSL-10-1, qSW-4-1, qSV-4-1, qSLW-10-1, and qSLH-10-1. Thirteen of the 42 QTLs detected in the current study were found at known loci, while the remaining 29 were discovered for the first time. Out of these 29 novel QTLs, 17 were major QTLs. Based on Protein Analysis Through Evolutionary Relationships (PANTHER), gene annotation information, and literature search, 66 genes within seven stable QTLs were predicted to be possible candidate genes that might regulate seed shape and seed weight in soybean. The current study identified the key candidate genes and quantitative trait loci (QTLs) controlling soybean seed shape and weight, and these results will be very helpful in marker-assisted breeding for developing soybean varieties with improved seed weight and desired seed shape.

Dopamine ß hydroxylase as a potential drug target to combat hypertension.

INTRODUCTION: Despite a large number of commercially available drugs, hypertension and related cardiovascular diseases remain a global problem. It is thus imperative that novel drugs and therapeutic strategies are regularly identified, and alternative targets explored. Dopamine ß hydroxylase (DBH), a key player in the catecholamine biosynthetic pathway, may provide a therapeutic opportunity and should be extensively explored as a target for potent anti-hypertensives. Inhibitors of DBH have been successful in combating hypertension, as evidenced by the outcome of clinical trials for etamicastat and zamicastat. AREAS COVERED: We shed light on the strategies employed to identify inhibitors of the enzyme and outline the advantages that the target might offer. Structural and functional details of the enzyme are described along with specific methodologies for drug discovery that were never utilized for the therapeutic target. EXPERT OPINION: Effective inhibitors of the enzyme may be identified with computer-aided structure-based design. Adoption of new methodologies and the assessment of newly designed inhibitors in DBH-specific animal models will provide new, safe, and cost-effective therapeutic opportunities.

Design, synthesis and biological evaluation of antimalarial activity of new derivatives of 2,4,6-s-triazine.

Dihydrofolate reductase (DHFR) is an important enzyme for de novo synthesis of nucleotides in Plasmodium falciparum and it is essential for cell proliferation. DHFR is a well known antimalarial target for drugs like cycloguanil and pyrimethamine which target its inhibition for their pharmacological actions. However, the clinical efficacies of these antimalarial drugs have been compromising due to multiple mutations occurring in DHFR that lead to drug resistance. In this background, we have designed 22 s -triazine compounds using the best five parameters based 3D-QSAR model built by using genetic function approximation. In-silico designed compounds were further filtered to 6 compounds based upon their ADME properties, docking studies and predicted minimum inhibitory concentrations (MIC). Out of 6 compounds, 3 compounds were synthesized in good yield over 95% and characterized using IR, 1HNMR, 13CNMR and mass spectroscopic techniques. Parasitemia inhibition assay was used to evaluate the antimalarial activity of s -triazine compounds against 3D7 strain of P. falciparum. All the three compounds (7, 13 and 18) showed 30 times higher potency than cycloguanil (standard drug). It was observed that compound 18 was the most active while the compound 13 was the least active. On the closer inspection of physicochemical properties and SAR, it was observed that the presence of electron donating groups, number of hydrogen bond formation, lipophilicity of ligands and coulson charge of nitrogen atom present in the triazine ring enhances the DHFR inhibition significantly. This study will contribute to further endeavours of more potent DHFR inhibitors.

Evaluation of Systemic Antioxidant Level and Oxidative Stress in Relation to Lifestyle and Disease Progression in Asthmatic Patients.

BACKGROUND: Asthma is a chronic disorder of the airways. Oxidative stress is an important part of asthma pathogenesis. It plays a crucial role in exacerbating the disease, as well as an important consequence of airways inflammation. AIM: The present study was undertaken to investigate the lipid peroxidation and catalase activity in serum and antioxidant level in plasma of asthmatic patients and their association with lifestyle and severity of the disease. METHODS: A total of 210 subjects, 120 asthmatics and 90 healthy controls matched in respect to age, sex, lifestyle and socioeconomic status, were chosen randomly for the present study. The samples were analyzed for MDA concentration and catalase activity in serum and ferric reducing ability of plasma (FRAP). Statistical analysis was done using unpaired Student's t-test, ANOVA with Duncan post hoc test and Pearson coefficient of correlation. RESULTS: The serum MDA was found to be significantly higher in the asthmatics as compared to healthy individuals (p<0.01) while catalase activity in serum and antioxidant level of the plasma were markedly lower in the asthmatics as compared to healthy individuals (p<0.01). A significant difference was observed in serum MDA, catalase activity and plasma antioxidant level among the patients in relation to the severity of disease. There was a marked increase in the serum MDA in the patients with longer duration of the disease (p<0.05). CONCLUSIONS: The oxidant-antioxidant imbalance occurs in asthma leading to oxidative stress and is an important part of the asthma pathogenesis.

Chronic, highly productive HIV infection in monocytes during supportive culture.

Peripheral blood monocytes of HIV-infected individuals carry virus, constituting one potential reservoir. However, most studies of infection in tissue culture find monocytes refractory to HIV replication, suggesting that culture conditions limit the relative susceptibility of this target cell. We employed a tissue culture system optimized for maintenance of human monocytes without differentiation and compared HIV infection efficiency of monocytes and fully differentiated monocyte derived macrophages (MDM). We tested direct virus-cell fusion, expression of cell lineage markers, and productive HIV infection in fresh monocytes, monocytes after varying periods of supportive culture, and fully differentiated MDM comparing cells from individual donors. Fresh, uncultured monocytes allowed modest HIV fusion, however one week culture was sufficient to allow efficient fusion and an increase in expression of CD14, CD16, CD33, and CD105. Compared to freshly isolated monocytes, monocytes infected after a few days in culture produced p24 more quickly, but the peaks of production were similar. Fresh monocytes were highly susceptible to productive HIV infection in supportive culture, roughly equal to MDM from the same donor in expression of extracellular p24 up to five weeks after infection. Taken together our findings indicate that monocytes are biologically capable of supporting chronic, highly productive HIV infection, a capacity that may reflect their status in HIV-infected persons.