Low frequency of regulatory B-cells and increased CD4+ and CD8+ interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type

Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.

Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

To evaluate factors associated with human immunodeficiency virus type 1 (HIV-1) proviral DNA load, we conducted a cross-sectional study of 36 chronically HIV-1- infected individuals with undetectable plasma viral RNA. We used real-time polymerase chain reaction to determine the number of HIV-1 proviral DNA copies per 10(6) peripheral blood mononuclear cells. The mean level of plasma viral RNA when the CD4+ T cell count was above 500 cells/microliter without highly active antiretroviral therapy (HAART) was significantly associated with proviral DNA load at the time of undetectable plasma HIV RNA with HAART. Strategies to reduce the level of plasma viral RNA when patients' CD4+ T cell counts are above 500 cells/microliter without HAART could help reduce HIV-1 proviral DNA load.

Structural biology of chemokine receptors

Chemokine receptors are G protein-coupled receptors that mediate migration and activation of leukocytes as an important part of a protective immune response to injury and infection. In addition, chemokine receptors are used by HIV-1 to infect CD4 positive cells. The structural bases of chemokine receptor recognition and signal transduction are currently being investigated. High-resolution X-ray diffraction and NMR spectroscopy of chemokines indicate that all these peptides exhibit a common folding pattern, in spite of its low degree of primary-sequence homology. Chemokines' functional motifs have been identified by mutagenesis studies, and a possible mechanism for receptor recognition and activation is proposed, but high-resolution structure data of chemokine receptors is not yet available. Studies with receptor chimeras have identified the putative extracellular domains as the major selectivity determinants. Single-amino acid substitutions in the extracellular domains produce profound changes in receptor specificity, suggesting that motifs in these domains operate as a restrictive barrier to a common activation motif. Similarly HIV-1 usage of chemokine receptors involves interaction of one or more extracellular domains of the receptor with conserved and variable domains on the viral envelope protein gp 120, indicating a highly complex interaction. Elucidating the structural requirements for receptor interaction with chemokines and with HIV-1 will provide important insights into understanding the mechanisms of chemokine recognition and receptor activation. In addition, this information can greatly facilitate the design of effective inmunomodulatory and anti-HIV-1 therapeutic agents

La dinámica del HIV y la restauración inmune: algunos avances y un gran desafío / The HIVïs dynamics and the immune restoration: some advances and a great challenge

Algunos descubrimientos recientes han permitido un mejor conocimiento de la fisiopatología de la enfermedad debida al HIV, lo que ha producido un cambio de las teorías hasta ahora aceptadas acerca de la replicación viral. De acuerdo con un modelo matemático recientemente desarrollado, la replicación viral alcanza proporciones astronómicas, lo que acompañado a numerosos errores que ocurren durante la transcripción del ARN permite la aparición de nuevas cuasi-especies. Las cepas mutantes son responsables en parte del fracaso de la monoterapia, hecho que es superado por la administración de tratamiento combinado que disminuye la replicación viral. Estos nuevos agentes terapéuticos han logrado aumentar el número de linfocitos TCD4(+) y reducir los niveles de la carga viral. Recientes publicaciones muestran que un pequeño grupo de pacientes presentaron infecciones oportunistas con un recuento de CD4 alto a pesar de estar recibiendo Terapéutica Antiviral Altamente Efectiva (HAART sus siglas en inglés). Por otro lado, algunos enfermos resolvieron sus patologías oportunistas a pesar de no recibir tratamiento específico contra las mismas, excepto HAART. Estos conceptos, y también otros referidos a la dinámica viral y la restauración inmune, son analizados en la presente revisión