Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling
© 2022. The Author(s)..
We previously showed that HIV-1 can alter the expression of tight junction proteins by downregulating Sonic hedgehog (Shh) signaling, thereby disrupting blood-brain barrier (BBB) integrity. In this study, we employed a conditional, CNS specific, Tat transgenic murine model to investigate if HIV-Tat exerts its neurotoxic effects by downregulating Shh signaling. Results indicate that Tat + mice exhibit significantly reduced expression of Shh and Gli1. HIV-Tat induced downregulation of Shh signaling correlated with disruption of BBB function and induced infiltration of peripheral leukocytes into the brain tissue. Further, our in vivo and in vitro experiments suggest that activation of Shh signaling can rescue detrimental effects of Tat on endothelial function by inducing the expression of junctional proteins and by decreasing the levels of inflammatory cytokines/chemokines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Journal of neurovirology - 28(2022), 2 vom: 01. Apr., Seite 305-311 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khan, Irfan A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.06.2022 Date Revised 21.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s13365-022-01061-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM337137102 |
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| 100 | 1 | |a Khan, Irfan A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling |
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| 500 | |a Date Revised 21.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a We previously showed that HIV-1 can alter the expression of tight junction proteins by downregulating Sonic hedgehog (Shh) signaling, thereby disrupting blood-brain barrier (BBB) integrity. In this study, we employed a conditional, CNS specific, Tat transgenic murine model to investigate if HIV-Tat exerts its neurotoxic effects by downregulating Shh signaling. Results indicate that Tat + mice exhibit significantly reduced expression of Shh and Gli1. HIV-Tat induced downregulation of Shh signaling correlated with disruption of BBB function and induced infiltration of peripheral leukocytes into the brain tissue. Further, our in vivo and in vitro experiments suggest that activation of Shh signaling can rescue detrimental effects of Tat on endothelial function by inducing the expression of junctional proteins and by decreasing the levels of inflammatory cytokines/chemokines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Blood–brain barrier | |
| 650 | 4 | |a HAND (HIV-associated neurocognitive disorder) | |
| 650 | 4 | |a HIV-Tat | |
| 650 | 4 | |a Neuroinflammation | |
| 650 | 4 | |a Sonic hedgehog | |
| 650 | 7 | |a Hedgehog Proteins |2 NLM | |
| 650 | 7 | |a Shh protein, mouse |2 NLM | |
| 650 | 7 | |a tat Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 700 | 1 | |a Worrad, Arthur H |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Meera V |e verfasserin |4 aut | |
| 700 | 1 | |a Maggirwar, Sanjay B |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Vir B |e verfasserin |4 aut | |
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