HIV Alters Gap Junction-Mediated Intercellular Communication in Human Brain Pericytes

Area of Science:

• Neuroscience
• Infectious Diseases
• Cell Biology

Background:

• Human immunodeficiency virus (HIV) infection can lead to neurocognitive impairment due to brain invasion and blood-brain barrier (BBB) dysfunction.
• The role of pericytes in BBB regulation during HIV infection is not well understood, although some pericytes are susceptible to infection.

Purpose of the Study:

• To investigate the role of gap junction (GJ)-mediated intercellular communication in the propagation of HIV infection in brain pericytes.
• To determine if HIV infection alters GJ protein expression and function in pericytes.

Main Methods:

• Immunoblotting and immunostaining to assess connexin 43 (Cx43) expression in HIV-infected human brain pericytes and in mouse brains infected with EcoHIV.
• Functional assays to measure GJ-mediated intercellular communication in pericytes.
• Experiments using carbenoxolone to inhibit GJs and assess its effect on HIV infection.
• Extracellular ATP release assays to investigate connexin (Cx)-containing hemichannel (HC) activity.

Main Results:

• HIV infection specifically increased Cx43 expression in human brain pericytes and in mouse brains.
• HIV infection enhanced functional GJ-mediated intercellular communication in pericytes.
• Inhibition of GJs by carbenoxolone attenuated HIV infection.
• HIV infection may also promote the opening of Cx-containing hemichannels.

Conclusions:

• Gap junctions play a significant role in the propagation of HIV infection within human brain pericytes.
• Altered GJ communication and hemichannel activity in pericytes may contribute to blood-brain barrier dysfunction and the pathogenesis of NeuroAIDS.