HIV-1 Tat Activates Neuronal Ryanodine Receptors with Rapid Induction of the Unfolded Protein Response and Mitochondrial Hyperpolarization
2008

HIV-1 Tat and Neuronal Stress

publication 10 minutes Evidence: moderate

Author Information

Author(s): Norman John P., Perry Seth W., Reynolds Holly M., Kiebala Michelle, De Mesy Bentley Karen L., Trejo Margarita, Volsky David J., Maggirwar Sanjay B., Dewhurst Stephen, Masliah Eliezer, Gelbard Harris A.

Primary Institution: University of Rochester School of Medicine and Dentistry

Hypothesis

Does HIV-1 Tat induce stress responses in neurons through ryanodine receptor activation?

Conclusion

HIV-1 Tat activates neuronal stress responses, leading to mitochondrial dysfunction and endoplasmic reticulum pathology.

Supporting Evidence

  • HIV-1 Tat induces rapid loss of ER calcium in cortical neurons.
  • Ryanodine receptor antagonism mitigates Tat-induced mitochondrial hyperpolarization.
  • Ultrastructural studies show abnormal mitochondria and dilated ER in HIV-1 infected brain tissue.

Takeaway

HIV-1 Tat can harm brain cells by causing stress that messes up their energy production and communication.

Methodology

The study used in vitro and in vivo models to assess the effects of HIV-1 Tat on neuronal calcium signaling and stress responses.

Limitations

The study primarily focused on in vitro models, which may not fully replicate in vivo conditions.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0003731

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication