Potential Advantages of a Well-balanced Nutrition Regimen for People Living with Human Immunodeficiency Virus Type -1.

This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). Our review advocates for the integration and implementation of personalized nutritional assessments into the care plan for PLWH, proposing actionable strategies for healthcare providers in HIV-1 field.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study.

Background: The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the mechanisms remain unclear. The difficulty in elucidating the evolutionary origin of the earliest X4 viruses limits our understanding of this phenomenon.

Methods: We tracked the evolution of the transmitted/founder (T/F) HIV-1 in RV217 participants identified in acute infection.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort.

Type I IFN Derived from Ly6C Monocytes Suppresses Type 2 Inflammation in a Murine Model of Atopic Dermatitis.

The roles of innate immune cells, including eosinophils, basophils, and group 2 innate lymphoid cells, in atopic dermatitis (AD) have been well-documented, whereas that of monocytes, another component of the innate immunity, remains rather poorly understood, thus necessitating the topic of this study. In addition, cytokines and cellular pathways needed for the resolution of type 2 inflammation in AD need further investigation. Using a murine AD model, we report here that (i) Ly6C monocytes were rapidly recruited to the AD lesion in a CCR2-dependent manner, blockade of which exacerbated AD; (ii) type I IFN production is profoundly involved in this suppression because the blockade of it by genetic depletion or antibody neutralization exacerbated AD; and (iii) Ly6C monocytes operate through the production of type I IFN because Ly6C monocytes from Irf7-null mice, which lack type I IFN production, failed to rescue Ccr2 mice from severe AD upon adoptive transfer.

Effective treatment with the selective cytokine inhibitor BNZ-1 reveals the cytokine dependency of T-LGL leukemia.

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies.

Accessory cells precondition naïve T cells and regulatory T cells for cytokine-mediated proliferation.

Naïve T cells and regulatory T cells, when purified, do not proliferate to the γ-cytokines IL-2, IL-7, or IL-15, despite their expression of cognate cytokine receptors. Dendritic cells (DCs) enabled the T cell proliferation to these cytokines, through cell-to-cell contact, but independent of T cell receptor stimulation. This effect lasted after separation of T cells from DCs, enabling enhanced proliferation of the T cells in DC-depleted hosts.

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting.

The CCR5 (R5) to CXCR4 (X4) coreceptor switch in natural HIV-1 infection is associated with faster progression to AIDS, but the underlying mechanisms remain unclear. The difficulty in capturing the earliest moment of coreceptor switch limits our understanding of this phenomenon. Here, by tracking the evolution of the transmitted/founder (T/F) HIV-1 in a prospective cohort of individuals at risk for HIV-1 infection identified very early in acute infection, we investigated this process with high resolution.

Coagulation potential and the integrated omics of extracellular vesicles from COVID-19 positive patient plasma.

Extracellular vesicles (EVs) participate in cell-to-cell communication and contribute toward homeostasis under physiological conditions. But EVs can also contribute toward a wide array of pathophysiology like cancer, sepsis, sickle cell disease, and thrombotic disorders. COVID-19 infected patients are at an increased risk of aberrant coagulation, consistent with elevated circulating levels of ultra-high molecular weight VWF multimers, D-dimer and procoagulant EVs.

Reflections on Some of the Exceptional Features of HTLV-1 and HTLV-1 Research: A Perspective.

The report is not a review or a summary. In a manner, it is a perspective but an unusual one. It looks back to the years my colleagues and I (RG) began preparing for human retroviruses (beginning in 1970), how they evolved, and attempts to bring to light or simply to emphasize many exceptional characteristics of a retrovirus known as HTLV-1 and some fortuitous coincidences, with emphasis on the needs of the field.

Identifying CCR5 coreceptor populations permissive for HIV-1 entry and productive infection: implications for in vivo studies.

Background: The chemokine receptor CCR5 is the major coreceptor for HIV-1 cell entry. We previously observed that not all CCR5 mAbs reduce HIV-1 infection, suggesting that only some CCR5 populations are permissive for HIV-1 entry. This study aims to better understand the relevant conformational states of the cellular coreceptor, CCR5, involved in HIV entry.

Combined cART including Tenofovir Disoproxil, Emtricitabine, and Dolutegravir has potent therapeutic effects in HIV-1 infected humanized mice.

HIV-1 reservoirs persist in the presence of combined antiretroviral therapy (cART). However, cART has transformed HIV-1 infection into a chronic disease marked by control of HIV-1 viral load and mortality reduction. Major challenges remain, including viral resistance upon termination of cART and persistence and identification of tissue distribution of HIV-1 reservoirs.

Inflammatory monocyte-derived dendritic cells mediate autoimmunity in murine model of systemic lupus erythematosus.

Using a mouse model of systemic lupus erythematosus (SLE), we recently demonstrated that the two major manifestations of SLE are mechanistically independent because the type I IFN pathway leads to the autoantibody production whereas the NF-κB activation is sufficient for the development of glomerulonephritis. To further advance our understandings on the molecular pathways regulating the development of SLE, we studied the role of IRF8 because it controls both type I IFN and NF-κB pathways and saw that IRF8-deficient mice failed to develop either glomerulonephritis or the autoantibody production. Furthermore, these genetically engineered mice prompted us to realize the important role of Ly6C inflammatory monocytes in the development of SLE.

Anti-HIV Activity of Standard Combined Antiretroviral Therapy in Primary Cells Is Intensified by CCR5-Targeting Drugs.

The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission, and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment interruption. Efforts are ongoing to explore the most effective means to intensify cART and successfully control residual viral replication.

Identification of a γc Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21.

Background & Aims: Gamma chain (γc) cytokines (interleukin [IL]2, IL4, IL7, IL9, IL15, and IL21) signal via a common γc receptor. IL2 regulates the immune response, whereas IL21 and IL15 contribute to development of autoimmune disorders, including celiac disease. We investigated whether BNZ-2, a peptide designed to inhibit IL15 and IL21, blocks these cytokines selectively and its effects on intraepithelial cytotoxic T cells.

Results From a First-in-Human Study of BNZ-1, a Selective Multicytokine Inhibitor Targeting Members of the Common Gamma (γc) Family of Cytokines.

Pathologic roles of interleukin (IL)-2, IL-9, and IL-15, have been implicated in multiple T-cell malignancies and autoimmune diseases. BNZ-1 is a selective and simultaneous inhibitor of IL-2, IL-9, and IL-15, which targets the common gamma chain signaling receptor subunit. In this first-in-human study, 18 healthy adults (n = 3/cohort) received an intravenous dose of 0.

Suppression of Active HIV-1 Infection in CD34 Hematopoietic Humanized NSG Mice by a Combination of Combined Antiretroviral Therapy and CCR5 Targeting Drugs.

Significant progress has been made in the diagnostics and treatment of AIDS since the discovery of the human immunodeficiency virus type 1 (HIV-1) in 1983. The remarkable effectiveness of combined antiretroviral therapy (cART) is evidenced by mortality reduction, control of peripheral blood viral load, and in a nearly normal quality of HIV patients' lives. Remaining obstacles in treatment and cure are drug toxicities and side effects, viral resistance, persistence of HIV-1 reservoirs on termination of cART treatment, the cost of lifelong antiretroviral therapy, and the stigma associated with taking antiretroviral drugs.

40 years of the human T-cell leukemia virus: past, present, and future.

It has been nearly 40 years since human T-cell leukemia virus-1 (HTLV-1), the first oncogenic retrovirus in humans and the first demonstrable cause of cancer by an infectious agent, was discovered. Studies indicate that HTLV-1 is arguably one of the most carcinogenic agents to humans. In addition, HTLV-1 causes a diverse array of diseases, including myelopathy and immunodeficiency, which cause morbidity and mortality to many people in the world, including the indigenous population in Australia, a fact that was emphasized only recently.

IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective γ-chain cytokines, decreases leukemic T-cell viability.

Interleukin-15 (IL-15) and IL-2 drive T-cell malignancies including T-cell large granular lymphocyte leukemia (T-LGLL) and HTLV-1 driven adult T-cell leukemia (ATL). Both cytokines share common γ-chain receptors and downstream signaling pathways. T-LGLL is characterized by clonal expansion of cytotoxic T cells and is associated with abnormal JAK/STAT signaling.

The Exceptional Oncogenicity of HTLV-1.

Human T-cell leukemia virus-1 (HTLV-1) is the first pathogenic human retrovirus identified in 1979 by the Gallo group. HTLV-1 causes fatal T-cell leukemia (adult T cell leukemia) and a progressive myelopahy (HTLV-1-associated myelopathy/ tropical spastic paraparesis, HAM/TSP) and other disorders. Since the discovery of HTLV-1, several other microorganisms are demonstrated to cause cancer in humans.

Functional polymorphisms in rhesus macaque FCGRT and β2-m.

Rhesus macaque is an important animal model for studies testing interventions like antibody therapeutics; as such knowledge of inter-individual variations in function of genes affecting antibody recycling is important for optimal experimental design. Neonatal Fc receptor (FcRn), a heterodimer composed of FCGRT and β2-m chains, plays critical role in extending catabolic half-life of IgG. We studied genomic polymorphisms in rhesus macaque FcRn and asked if they are functional by assessing correlations with serum IgG or β2-m levels.