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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies. [ABSTRACT FROM AUTHOR]

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. Image 1 • Increase in levels of intracellular cAMP reactivates HIV in latently infected U1 cells. • PDE inhibitor drugs enhance HIV reactivation in myeloid cells and can be further explored for latency reversal properties. • cAMP modulates transcriptional profile of latently HIV-infected monocytes. • cAMP reverses HIV latency in myeloid cells through transcription factor Sp1. [ABSTRACT FROM AUTHOR]