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Tytuł pozycji:

Neurotoxicity of HIV-1 Tat is attributed to its penetrating property.

Tytuł:
Neurotoxicity of HIV-1 Tat is attributed to its penetrating property.
Autorzy:
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. .
Źródło:
Scientific reports [Sci Rep] 2020 Aug 19; Vol. 10 (1), pp. 14002. Date of Electronic Publication: 2020 Aug 19.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Dependovirus/*genetics
Exosomes/*genetics
Genetic Vectors/*genetics
Neurons/*metabolism
tat Gene Products, Human Immunodeficiency Virus/*genetics
Animals ; Brain/metabolism ; Brain/virology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/virology ; Cell Line, Tumor ; Cell Survival/genetics ; Gene Expression ; Genetic Vectors/blood ; Genetic Vectors/pharmacokinetics ; HEK293 Cells ; Humans ; Injections, Intravenous ; Liver/metabolism ; Liver/virology ; Mice, Inbred BALB C ; Neurons/cytology ; Synaptic Membranes/metabolism ; Synaptic Membranes/virology ; Synaptophysin/genetics ; Synaptophysin/metabolism ; Transfection/methods ; tat Gene Products, Human Immunodeficiency Virus/blood ; tat Gene Products, Human Immunodeficiency Virus/metabolism
References:
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Grant Information:
R01 HD072693 United States HD NICHD NIH HHS; P30 GM110759 United States GM NIGMS NIH HHS; K24 HD080539 United States HD NICHD NIH HHS; U54 GM115677 United States GM NIGMS NIH HHS; P01 AA019072 United States AA NIAAA NIH HHS; P30 AI042853 United States AI NIAID NIH HHS
Substance Nomenclature:
0 (Synaptophysin)
0 (tat Gene Products, Human Immunodeficiency Virus)
Entry Date(s):
Date Created: 20200821 Date Completed: 20201223 Latest Revision: 20210819
Update Code:
20240105
PubMed Central ID:
PMC7438513
DOI:
10.1038/s41598-020-70950-x
PMID:
32814783
Czasopismo naukowe
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.
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