New insights on the perturbations of T cell cycle during HIV infection.
The role of the Human Immunodeficiency Virus (HIV) in the pathogenesis of the Acquired Immune-Deficiency Syndrome (AIDS) is changed. Direct HIV-mediated killing of CD4(+) T cells is not the only mechanism leading to lymphocyte depletion. There is increasing evidence that, during the chronic phases of infection, T cell activation, accelerated cell turnover, and cytokines imbalance induce the so-called cell cycle dysregulation (CCD). CCD is a recently discovered immune-pathogenic mechanism that mainly induces the depletion of both CD4(+) and CD8(+) uninfected T cells. It is due to a significant perturbation of protein metabolism as ubiquitin pathway defects of protein degradation are associated with an increased and unscheduled expression of cyclin B and p34 cdc kinase. Moreover, significant changes in the nucleolar structure and post-translational regulation of nucleolin have also been described. As modulation of CCD by anti-retroviral and immune-therapies has been suggested to predict a good immunological response in HIV-infected patients, a better understanding of such a mechanism is needed in order to further clarify its role in the pathogenesis and progression of HIV infection.
Galati
Domenico
D
Department of Pathology, University of Naples Federico II, Naples, Italy. dgalati@tiscali.it
Bocchino
Marialuisa
M
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology / Q000502:physiology*; D019926:Cyclin B / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D025801:Ubiquitin / Q000378:metabolism*; D000097796:Nucleolin
D019380:Anti-HIV Agents; D016203:CDC2 Protein Kinase; D019926:Cyclin B; D016207:Cytokines; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D000097796:Nucleolin