Signatures of HIV-1 subtypes, Tat proteins and their effects in neuropathogenesis of HIV-associated neurocognitive impairments

  • Heather Mason
  • Medical News
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HIV-associated neurocognitive impairments (HANI) are a spectrum of neurological disorders due to the effect of HIV-1 on the central nervous system (CNS). HANI is complex and affected by several factors which may include the HIV-1 subtype, although to what extent remains unclear. Severity ranges from asymptomatic to mild and the most severe form, HIV-associated dementia. 

There is a strong research interest in understanding the neuropathological mechanisms induced by Trans-activator of transcription (Tat), which acts as an RNA specific viral transcription factor, as its secretion persists despite viral suppression. 

This review article discusses Tat-subtype variations that contribute to the underlying neurobiological mechanisms of HANI. Amino acid variations between HIV-1B Tat (Tat-B) and HIV-1C Tat (Tat-C) proteins induce differences in transcriptional capacity, transactivation capacity, immune regulation, and neuronal damage pathways.

Tat dysregulates the Kynurenine pathway and the calcium ion regulation in the glutamatergic system, and alters synaptic plasticity and neuron morphology. Tat protein is also responsible for chemotactic events which may lead to a dysregulation of cytokines, contributing to the neuropathophysiology of HANI.

The HIV-1 subtype B (HIV-1B) is present in America, Western Europe and Australasia and represents 12% of all HIV infections, whereas HIV-1 subtype C (HIV-1C) is present in Southern Africa and India and represents 50% of the world’s HIV population. Pre-clinical studies suggest an increased neurovirulence for HIV-1B with a higher prevalence of HANI, although recent studies provide contradictory findings. 

Key points;

  • The HIV Tat protein is a major viral determinant in HANI development.
  • Tat-B and Tat-C differ biologically.
  • The extent to which Tat sequence variation affects neurovirulence and neurological outcomes requires further investigation. 
  • This review identifies key protein sequence differences which may account for altered neuropathogenesis.