Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs).

HIV proviral reservoirs are cells that harbour integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern therapies that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction of the proviral reservoir pool in the early stages of the disease. HIV subtype provides differences in the number of latent reservoirs among different subtypes, as determined by structural and functional differences. Unique phenotypes of HIV-infected patients, such as elite controllers, have control over viral replication and can be said to have achieved functional cure of HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which are CRSPR/cas9, “Shock and kill” and “Block and lock”.

Developed by the European Society of Cardiology (ESC) Peripheral Arterial and Aortic Disease Task Force in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS), with special input from the ESC European Association for Rare Multisystemic Vascular Diseases (VASCERN) and the European Society for Vascular Medicine (ESVM). Lucia Mazzolai, Gisela Teixido-Tura, Stefano Lanzi, Vinko Boc, Eduardo Bossone, Marianne Brodmann, Alessandra Bura-Rivière, Julie De Backer, Sebastien Deglise, Alessandro Della Corte, Christian Heiss, Marta Kałużna-Oleksy, Donata Kurpas, Carmel M McEniery, Tristan Mirault, Agnes A Pasquet, Alex Pitcher, Hannah A I Schaubroeck, Oliver Schlager, Per Anton Sirnes, Muriel G Sprynger, Eugenio Stabile, Françoise Steinbach, Matthias Thielmann, Roland R J van Kimmenade, Maarit Venermo, Jose F Rodriguez-Palomares, ESC Scientific Document Group. Full text of the guideline is published: European Heart Journal, Volume 45, Issue 36, September 21, 2024, Pages 3538-3700, https://doi.org/10.1093/eurheartj/ehae179

Determining HIV-1 tropism provides the prognosis of HIV infection and is required before prescribing maraviroc, an entry inhibitor that blocks the interaction between the viral gp120 and the CCR5 coreceptor. However, existing prediction algorithms have been developed primarily for the globally most prevalent subtypes (B, C, and CRF01_AE) and often show reduced performance for other HIV-1 genetic variants. Sub-subtype A6 and circulating recombinant form CRF63_02A6 dominate the HIV-1 epidemic in Russia and other Former Soviet Union (FSU) countries, yet the reliability of tropism prediction for these viruses remains virtually unexplored. We phenotypically determined the tropism of 25 clinical isolates (11 R5, 1 X4, and 7 dual-tropic R5/X4) using U87.CD4.CCR5 and U87.CD4.CXCR4 cell lines and performed a comparative analysis of eight existing genotypic tools (Geno2pheno, WebPSSM, T-CUP 2.0, the Delobel/Garrido rules, and others) or their modifications on a combined dataset that included Los Alamos National Laboratory (LANL) reference sequences (subtypes A, B, C, CRF01_AE, and CRF02_AG) and our laboratory-derived isolates. Most models achieved high accuracy for globally prevalent subtypes (≈95% for B, C, and CRF01_AE) but showed markedly reduced performance for sub-subtype A6 (best accuracy among existing models, 85%) and CRF63_02A6 (best accuracy, 72%), with a poor balance between sensitivity and specificity. To address this problem, we developed HIV-V3Augur, an ensemble stacking model based on the Random Forest and Support Vector Machine (SVM) machine learning algorithms, trained on Pseudo Amino Acid Composition (PseAAC) and Relative Synonymous Codon Usage (RSCU) features with 10-fold stratified cross-validation. HIV-V3Augur achieved an accuracy of 77%, sensitivity of 79%, and specificity of 79% on sub-subtype A6, and on CRF63_02A6 it reached an accuracy of 95%, sensitivity of 87%, and specificity of 100%. Cross-validation demonstrated that HIV-V3Augur represents a balanced genotypic tropism prediction tool for understudied HIV-1 variants circulating in the FSU region. HIV-V3Augur can be used locally through a graphical user interface.

We present the single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMC) from individuals during acute HIV-1 infection caused by viral strains circulating in Russia and the Former Soviet Union (FSU) countries. Using 10x Genomics single-cell RNA sequencing (scRNA-seq) on the Illumina NextSeq 550 platform, we have analyzed scRNA-seq data from three treatment-naive patients (viral load > 1 × 10⁶ copies/mL, estimated infection duration ≤ 4 weeks) and three healthy donors. Data integration (Seurat, Harmony), automated cell-type annotation (CellTypist), and GeneOntology (GO) enrichment analysis for highly expressed and low-expressed genes revealed a profound reorganization of transcriptional programs across key immune populations, including memory CD4⁺ and CD8⁺ T cells, non-classical monocytes and natural killer cells (NK-cells). We observed signatures of hyperactivation of pro-inflammatory pathways (NF-kB, TNF, and type I/II interferon signaling), upregulation of genes associated with cellular migration (CXCR4, CCR7) and metabolic adaptation (oxidative phosphorylation components), alongside a mixed pro- and anti-apoptotic expression profile. Notably, our data pointed to a pronounced dysregulation of the TGF-β and mTOR signaling cascades, disrupted intercellular communication networks—particularly between cytotoxic cells and their regulators—altered expression of genes implicated in disease progression (OLR1, SERPINB2, COPS9) and viral persistence control (NEAT1, NAF1). This work provides an initial single-cell transcriptional atlas characterizing early immune responses to HIV-1 sub-subtypes A6 and CRF63_02A6, the predominant drivers of the HIV epidemic across the FSU region.

A prototype of a multiplex digital PCR (dPCR) test system was developed and analytically validated for absolute quantification of bovine leukemia virus (BLV) proviral load with normalization to the cellular DRA gene. The study was conducted on a sample of 90 cattle from farms in Novosibirsk Oblast and the Republic of Dagestan with established virus genotypes (G4 or G7) and aged 3 months to 12 years. For quantitative assessment of proviral DNA, multiplex dPCR with the EcoRI r estriction enzyme was used on the QIAcuity platform (Qiagen, Germany). Analytical sensitivity was assessed in accordance with the CLSI EP17‐A2 protocol, determining the limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ). The developed dPCR system provides separate detection of the BLV pol gene (FAM channel) and the cellular DRA gene (HEX channel). Analytical characteristics were established: LoB – 5 positive droplets, LoD – 1.3–1.5 copies/well (95%), LoQ – 10 copies/well (CV = 15.2%). A 7.1‐fold higher median proviral load (PVL) was shown in animals with genotype G4 (324,295 copies/10^6 cells) compared to G7 (45,420 copies/10^6 cells). A trend of increasing PVL with animal age was revealed: from 95,872 (G4) and 48,786 (G7) in the 1–3‐year age group to 363,837 (G4) in the 9–10‐year group. The developed prototype of the dPCR test system provides sensitive and quantitatively reproducible determination of BLV proviral load, which allows more accurate identification of high epizootic risk groups and monitoring of infection dynamics at the herd level. For the first time, quantitative differences in PVL between G4 and G7 BLV genotypes were documented.