| Autor: |
Tang X; Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of Brown University, 55 Claverick Street (Laboratory 414), Providence, RI, 02903, USA., Lu H; Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of Brown University, 55 Claverick Street (Laboratory 414), Providence, RI, 02903, USA., Ramratnam B; Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Rhode Island Hospital and Warren Alpert Medical School of Brown University, 55 Claverick Street (Laboratory 414), Providence, RI, 02903, USA. BRamratnam@Lifespan.org. |
| Abstrakt: |
We have recently engineered an exosomal Tat (Exo-Tat) which can activate latent HIV-1 in resting CD4+ T lymphocytes from antiretroviral treated HIV-1 infected patients. HIV-1 Tat protein can penetrate cell membrane freely and secrete into extracellular medium. Exo-Tat loses this penetrating property. HIV-1 Tat protein can damage the synaptic membranes contributing to the development of dementia in HIV-1 infected patients. To investigate whether the penetrating property attributes to synaptic damage in vivo, we have generated adeno-associated viruses AAV-Tat and AAV-Exo-Tat viruses. Vehicle control or AAV viruses (1 × 10 12 GC/mouse in 200 μl PBS) were injected into Balb/cj mice via tail veins. The mRNA and protein expression levels in blood, brain, heart, intestine, kidney, liver, lung, muscle and spleen were determined on day 21. Intravenously injected AAV-Tat or AAV-Exo-Tat mainly infects liver and heart. Short-term expression of Tat or Exo-Tat doesn't change the expression levels of neuronal cytoskeletal marker β3-tubulin and synaptic marker postsynaptic density 95 protein (PSD-95). Wild-type Tat, but not Exo-Tat, reduces the expression level of synaptic marker synaptophysin significantly in mice, indicating that penetrating property of HIV-1 Tat protein attributes to synaptic damage. |
