T cell activation andproliferation signaling, HIV
Since the advent of highly active anti-retroviral treatment (HAART), the average life expectancy of an HIV-infected patient has increased dramatically and reductions in viral loads have been achieved below limits of detection. A number of aspects in HIV infection have been accentuated by these successes, presenting new challenges to effective treatment of disease progression. The significance of latent reservoirs, particularly in CD4+ resting T cells, has become evident as these populations of long-lived and protected cells provide sanctuaries from which HIV can persist and reinitiate disease progression, even in patients treated with HAART. Recent data in our lab has indicated that the antibiotic minocycline, a derivative of tetracycline, may affect reactivation of HIV-1 from latently infected resting CD4+ T cells. FACS analysis shows that minocycline treatment decreases expression of markers for proliferation (Ki67) and activation (CD25) on latently infected resting T cells in response to activation signals; real time RT-PCR measurements of virus release show that minocycline has a suppressive effect on HIV replication. Ongoing studies will further investigate minocycline’s effect on regulatory mechanisms governing T cell activation and proliferation, as well as defining their link to HIV replication.
GL Szeto, AK Brice, HC Yang, SA Barber, RF Siliciano, JE Clements Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells Journal of Infectious Diseases 201 (8), 1132-1140
GL Szeto, JL Pomerantz, DRM Graham, JE Clements Minocycline suppresses activation of nuclear factor of activated T cells 1 (NFAT1) in human CD4+ T cells Journal of Biological Chemistry 286 (13), 11275-11282