Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Plasma Galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

OBJECTIVE: Adolescents with perinatally-acquired HIV (AWH) are at an increased risk of poor cognitive development but the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multi-morbidity in adults with HIV despite anti-retroviral therapy (ART), however, relationship between Gal-9 in AWH and cognition remain unexplored. DESIGN: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART (n = 15), ART-naïve (n = 15), and adolescents without HIV (AWOH; n = 10)] and Myanmar [AWH on ART (n = 54) and AWOH (n = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests. METHODS: Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning (ML) to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers. RESULTS: Gal-9 levels were elevated in ART-treated AWH compared to AWOH in both cohorts (all p < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 T cells (all p < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains (verbal learning, visuospatial learning, memory, motor skills (all p < 0.05). ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents (mean AUC = 0.837). CONCLUSION: Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

A bioinformatics approach to elucidate conserved genes and pathways in C. elegans as an animal model for cardiovascular research.

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in CVD research. Caenorhabditis elegans, a nematode species, has emerged as a prominent experimental organism widely utilized in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilization for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, and aha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signaling pathway, the FoxO signaling pathway, the MAPK signaling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.

Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases.

Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.

Identification of potential regulatory mechanisms and therapeutic targets for lung cancer.

Lung cancer poses a significant health threat globally, especially in regions like India, with 5-year survival rates remain alarmingly low. Our study aimed to uncover key markers for effective treatment and early detection. We identified specific genes related to lung cancer using the BioXpress database and delved into their roles through DAVID enrichment analysis. By employing network theory, we explored the intricate interactions within lung cancer networks, identifying ASPM and MKI67 as crucial regulator genes. Predictions of microRNA and transcription factor interactions provided additional insights. Examining gene expression patterns using GEPIA and KM Plotter revealed the clinical relevance of these key genes. In our pursuit of targeted therapies, Drug Bank pointed to methotrexate as a potential drug for the identified key regulator genes. Confirming this, molecular docking studies through Swiss Dock showed promising binding interactions. To ensure stability, we conducted molecular dynamics simulations using the AMBER 16 suite. In summary, our study pinpoints ASPM and MKI67 as vital regulators in lung cancer networks. The identification of hub genes and functional pathways enhances our understanding of molecular processes, offering potential therapeutic targets. Importantly, methotrexate emerged as a promising drug candidate, supported by robust docking and simulation studies. These findings lay a solid foundation for further experimental validations and hold promise for advancing personalized therapeutic strategies in lung cancer.Communicated by Ramaswamy H. Sarma.

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for Establishing Caenorhabditis elegans as an Animal Model for Cardiovascular Diseases.

Cardiovascular disease (CVD) is a collective term for disorders of the heart and blood vessels. The molecular events and biochemical pathways associated with CVD are difficult to study in clinical settings on patients and in vitro conditions. Animal models play a pivotal and indispensable role in cardiovascular disease (CVD) research. Caenorhabditis elegans , a nematode species, has emerged as a prominent experimental organism widely utilised in various biomedical research fields. However, the specific number of CVD-related genes and pathways within the C. elegans genome remains undisclosed to date, limiting its in-depth utilisation for investigations. In the present study, we conducted a comprehensive analysis of genes and pathways related to CVD within the genomes of humans and C. elegans through a systematic bioinformatic approach. A total of 1113 genes in C. elegans orthologous to the most significant CVD-related genes in humans were identified, and the GO terms and pathways were compared to study the pathways that are conserved between the two species. In order to infer the functions of CVD-related orthologous genes in C. elegans, a PPI network was constructed. Orthologous gene PPI network analysis results reveal the hubs and important KRs: pmk-1, daf-21, gpb-1, crh-1, enpl-1, eef-1G, acdh-8, hif-1, pmk-2, and aha-1 in C. elegans. Modules were identified for determining the role of the orthologous genes at various levels in the created network. We also identified 9 commonly enriched pathways between humans and C. elegans linked with CVDs that include autophagy (animal), the ErbB signalling pathway, the FoxO signalling pathway, the MAPK signalling pathway, ABC transporters, the biosynthesis of unsaturated fatty acids, fatty acid metabolism, glutathione metabolism, and metabolic pathways. This study provides the first systematic genomic approach to explore the CVD-associated genes and pathways that are present in C. elegans, supporting the use of C. elegans as a prominent animal model organism for cardiovascular diseases.

Microbiome analysis of saliva from oral squamous cell carcinoma (OSCC) patients and tobacco abusers with potential biomarkers for oral cancer screening.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and accounts for about 95% of all head and neck cancers with high mortality, usually at a late stage. Dysbiosis in the oral microbiome can lead to chronic inflammatory responses and may predispose to the development and progression of OSCC. Tobacco abuse plays an essential role in oral microbiome dysregulation and OSCC pathogenesis. We used 16S rRNA gene amplicon next-generation sequencing to examine microbial signatures unique to saliva from OSCC patients, tobacco abusers (TA) and controls (n = 10 for each group) to elucidate oral microbiome changes associated with tobacco abuse and OSCC. Overall, the oral microbiome compositions of class Betaproteobacteria and Epsilonproteobacteria, order Neisseriales, Burkholderiales and Campylobacterales, family Burkholderiaceae and Campylobacteraceae and genera Campylobacter and Leptotrichia revealed significant differences among OSCC patients, TA and control. Our preliminary pilot study not only serves as a basis for future studies with large sample size but also gives an indication of microbiome-based potential non-invasive biomarkers for early screening and monitoring of oral carcinogenesis transition due to tobacco abuse.

Exploring the Human Virome: Composition, Dynamics, and Implications for Health and Disease.

Humans are colonized by large number of microorganisms-bacteria, fungi, and viruses. The overall genome of entire viruses that either lives on or inside the human body makes up the human virome and is indeed an essential fraction of the human metagenome. Humans are constantly exposed to viruses as they are ubiquitously present on earth. The human virobiota encompasses eukaryotic viruses, bacteriophages, retroviruses, and even giant viruses. With the advent of Next-generation sequencing (NGS) and ongoing development of numerous bioinformatic softwares, identification and taxonomic characterization of viruses have become easier. The viruses are abundantly present in humans; these can be pathogenic or commensal. The viral communities occupy various niches in the human body. The viruses start colonizing the infant gut soon after birth in a stepwise fashion and the viral composition diversify according to their feeding habits. Various factors such as diet, age, medications, etc. influence and shape the human virome. The viruses interact with the host immune system and these interactions have beneficial or detrimental effects on their host. The virome composition and abundance change during the course of disease and these alterations impact the immune system. Hence, the virome population in healthy and disease conditions influences the human host in numerous ways. This review presents an overview of assembly and composition of the human virome in healthy asymptomatic individuals, changes in the virome profiles, and host-virome interactions in various disease states.

Biomanufacturing of glycosylated antibodies: Challenges, solutions, and future prospects.

Traditionally, recombinant protein production has been done in several expression hosts of bacteria, fungi, and majorly CHO (Chinese Hamster Ovary) cells; few have high production costs and are susceptible to harmful toxin contamination. Green algae have the potential to produce recombinant proteins in a more sustainable manner. Microalgal diversity leads to offer excellent opportunities to produce glycosylated antibodies. An antibody with humanized glycans plays a crucial role in cellular communication that works to regulate cells and molecules, to control disease, and to stimulate immunity. Therefore, it becomes necessary to understand the role of abiotic factors (light, temperature, pH, etc.) in the production of bioactive molecules and molecular mechanisms of product synthesis from microalgae which would lead to harnessing the potential of algal bio-refinery. However, the potential of microalgae as the source of bio-refinery has been less explored. In the present review, omics approaches for microalgal engineering, methods of humanized glycoproteins production focusing majorly on N-glycosylation pathways, light-based regulation of glycosylation machinery, and production of antibodies with humanized glycans in microalgae with a major emphasis on modulation of post-translation machinery of microalgae which might play a role in better understanding of microalgal potential as a source for antibody production along with future perspectives.

Cyanometabolites: molecules with immense antiviral potential.

Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc. Cyanometabolites classified as lectins include scytovirin (SVN), Oscillatoria agardhii agglutinin (OAAH), cyanovirin-N (CV-N), Microcystis viridis lectin (MVL), and microvirin (MVN) also possess a potent antiviral activity against viral diseases with unique properties to recognize different viral epitopes. Studies showed that a small linear peptide, microginin FR1, isolated from a water bloom of Microcystis species, inhibits angiotensin-converting enzyme (ACE), making it useful for the treatment of coronavirus disease 2019 (COVID-19). Our review provides an overview of the antiviral properties of cyanobacteria from the late 90s till now and emphasizes the significance of their metabolites in combating viral diseases, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has received limited attention in previous publications. The enormous medicinal potential of cyanobacteria is also emphasized in this review, which justifies their use as a dietary supplement to fend off pandemics in future.

Subtype diversity and emergence of drug resistance in HIV-1 in solapur district of Maharashtra, India.

Background and Objectives: Even after four decades, HIV infection remains a global challenge and a leading cause of mortality in adults across the world. Anti-retroviral therapy (ART) that controls HIV viremia, is now available through public health facilities in India but drug resistance, which is likely to develop among these individuals remains poorly studied in India. The objectives of present study are to find out the HIV-1 virus subtypes, drug resistance mutations and HIV-1 drug resistance to NRTI, NNRTI and protease inhibitors in the Solapur district, India. Materials and Methods: In a cross sectional study, forty two ART-experienced HIV-1-infected patients with CD4+ count < 200 cells ml-1 and viral load (VL) > 3, 000 copies ml-1 were recruited. All patients belonged to Maharashtra State of India near Barshi Solapur and had been on ART treatment for over 5 years. EDTA whole blood from HIV-1-infected patients was centrifuged and the viral nucleic acid was purified from the plasma. Viral nucleic acid was amplified by PCR using protease and reverse transcriptase specific primers. The resulting amplicons were sequenced and studied for mutations. The tools from Stanford University website were used for subtyping of HIV-1 and identification of mutations conferring drug resistance. Results: In present investigation, HIV-1 subtypes were subtype C in 37 (88.09%), subtype CRF01_AE in 2 (4.76%), and subtype A in 3 patients (7.14%). Drug resistance mutations of NRTI, NNRTI and protease were observed in 15 (37.71%) of 42 patients tested. Drug resistance for NRTI was observed in 12 (28.57%) and for NNRTI in 13 (30.95%) patients. No drug resistance was observed for protease inhibitors. Conclusion: Considerable HIV-1 drug resistance exists among patients receiving ART from a rural areas of India, suggesting more studies from rural region are required to prevent development of resistance to ART.

Process development and preclinical evaluation of a major Plasmodium falciparum blood stage vaccine candidate, Cysteine-Rich Protective Antigen (CyRPA).

Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) is an essential, highly conserved merozoite antigen that forms an important multi-protein complex (RH5/Ripr/CyRPA) necessary for erythrocyte invasion. CyRPA is a promising blood-stage vaccine target that has been shown to elicit potent strain-transcending parasite neutralizing antibodies. Recently, we demonstrated that naturally acquired immune anti-CyRPA antibodies are invasion-inhibitory and therefore a correlate of protection against malaria. Here, we describe a process for the large-scale production of tag-free CyRPA vaccine in E. coli and demonstrate its parasite neutralizing efficacy with commonly used adjuvants. CyRPA was purified from inclusion bodies using a one-step purification method with high purity (>90%). Biochemical and biophysical characterization showed that the purified tag-free CyRPA interacted with RH5, readily detected by a conformation-specific CyRPA monoclonal antibody and recognized by sera from malaria infected individuals thus indicating that the recombinant antigen was correctly folded and retained its native conformation. Tag-free CyRPA formulated with Freund's adjuvant elicited highly potent parasite neutralizing antibodies achieving inhibition of >90% across diverse parasite strains. Importantly, we identified tag-free CyRPA/Alhydrogel formulation as most effective in inducing a highly immunogenic antibody response that exhibited efficacious, cross-strain in vitro parasite neutralization achieving ~80% at 10 mg/ml. Further, CyRPA/Alhydrogel vaccine induced anti-parasite cytokine response in mice. In summary, our study provides a simple, scalable, cost-effective process for the production of tag-free CyRPA that in combination with human-compatible adjuvant induces efficacious humoral and cell-mediated immune response.

Super-rapid race for saving lives by developing COVID-19 vaccines.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people and claimed thousands of lives. Starting in China, it is arguably the most precipitous global health calamity of modern times. The entire world has rocked back to fight against the disease and the COVID-19 vaccine is the prime weapon. Even though the conventional vaccine development pipeline usually takes more than a decade, the escalating daily death rates due to COVID-19 infections have resulted in the development of fast-track strategies to bring in the vaccine under a year's time. Governments, companies, and universities have networked to pool resources and have come up with a number of vaccine candidates. Also, international consortia have emerged to address the distribution of successful candidates. Herein, we summarize these unprecedented developments in vaccine science and discuss the types of COVID-19 vaccines, their developmental strategies, and their roles as well as their limitations.

Galectin-9 as a biomarker of disease severity.

Galectin-9 (Gal-9) is a ß-galactoside binding lectin known for its immunomodulatory role in various microbial infections. Gal-9 is expressed in all organ systems and localized in the nucleus, cell surface, cytoplasm and the extracellular matrix. It mediates host-pathogen interactions and regulates cell signalling via binding to its receptors. Gal-9 is involved in many physiological functions such as cell growth, differentiation, adhesion, communication and death. However, recent studies have emphasized on the elevated levels of Gal-9 in autoimmune disorders, viral infections, parasitic invasion, cancer, acute liver failure, atopic dermatitis, chronic kidney disease, type-2 diabetes, coronary artery disease, atherosclerosis and benign infertility-related gynecological disorders. In this paper we have reviewed the potential of Gal-9 as a reliable, sensitive and non-invasive biomarker of disease severity. Tracking changes in Gal-9 levels and its implementation as a biomarker in clinical practice will be an important tool to monitor disease activity and facilitate personalized treatment decisions.

Heterogeneity Aware Two-Stage Group Testing.

Group testing refers to the process of testing pooled samples to reduce the total number of tests. Given the current pandemic, and the shortage of test supplies for COVID-19, group testing can play a critical role in time and cost efficient diagnostics. In many scenarios, samples collected from users are also accompanied with auxiliary information (such as demographics, history of exposure, onset of symptoms). Such auxiliary information may differ across patients, and is typically not considered while designing group testing algorithms. In this paper, we abstract such heterogeneity using a model where the population can be categorized into clusters with different prevalence rates. The main result of this work is to show that exploiting knowledge heterogeneity can further improve the efficiency of group testing. Motivated by the practical constraints and diagnostic considerations, we focus on two-stage group testing algorithms, where in the first stage, the goal is to detect as many negative samples by pooling, whereas the second stage involves individual testing to detect any remaining samples. For this class of algorithms, we prove that the gain in efficiency is related to the concavity of the number of tests as a function of the prevalence. We also show how one can choose the optimal pooling parameters for one of the algorithms in this class, namely, doubly constant pooling. We present lower bounds on the average number of tests as a function of the population heterogeneity profile, and also provide numerical results and comparisons.

Plasma metabolomic study in perinatally HIV-infected children using 1H NMR spectroscopy reveals perturbed metabolites that sustain during therapy.

BACKGROUND: Perinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease. OBJECTIVE: To elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children. METHOD: We have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation. RESULT: Validated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children. CONCLUSION: Developing therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.

Dichotomy of complement system: Tumorigenesis or destruction.

Complement system proteins, their regulators and endpoint effector complex significantly promote tumor growth by upregulation of oncogenic growth factors, activation of mitogenic signalling pathways and breakage of normal cell cycle. Contrastingly, complement cascades, initiated by anti-tumor therapeutic antibodies, also play a pivotal role in therapy response. This contradictory role of complement system possibly be a very crucial factor for the outcomes of antibody mediated immunotherapies. Herein, we reviewed the twin role of the complement system in cancer and also the genetic variations in complement system genes. Future studies should be focused on the biomarker discovery for the personalised cancer immunotherapies.

Transcriptional profiling indicates cAMP-driven reversal of HIV latency in monocytes occurs via transcription factor SP-1.

Latent HIV reservoir is a major barrier to absolute HIV cure. Studies on latency reversal agents (LRA) have by far focused mainly on CD4+ T-lymphocytes, while myeloid reservoirs remain under-represented despite their persistence and key contribution to HIV pathogenesis. cAMP has been shown to increase HIV-1 transcription in latently-infected monocytes/macrophages. In this communication, we explored the potential of commercially available pharmacological drugs and phosphodiesterase inhibitors to reactivate HIV in latently-infected monocytic cell-line, U1. We showed that increased levels of intracellular cAMP reverse HIV latency in vitro, which is specific to cells of the myeloid lineage. High throughput RNA-seq analysis revealed that cAMP modulates transcriptional profile of latently HIV-infected cells and provides favourable cellular environment for HIV to produce viral proteins. This reactivation of latent HIV was inhibited by Mithramycin A, a selective Sp1 inhibitor, indicating that the reversal of HIV latency in monocytes is driven by transcription factor Sp1.