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

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 × 1012 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Scientific reports - 10(2020), 1 vom: 19. Aug., Seite 14002

Sprache:

Englisch

Beteiligte Personen:

Tang, Xiaoli [VerfasserIn]
Lu, Huafei [VerfasserIn]
Ramratnam, Bharat [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, N.I.H., Extramural
Synaptophysin
Tat Gene Products, Human Immunodeficiency Virus

Anmerkungen:

Date Completed 23.12.2020

Date Revised 19.08.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-020-70950-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313886687