Drosophila model of anti-retroviral therapy induced peripheral neuropathy and nociceptive hypersensitivity

Abstract

The success of antiretroviral therapy (ART) has improved the survival of HIV-infected patients significantly. However, significant numbers of patients on ART whose HIV disease is well controlled show peripheral sensory neuropathy (PSN), suggesting that ART may cause PSN. Although the nucleoside reverse transcriptase inhibitors (NRTIs), one of the vital components of ART, are thought to contribute to PSN, the mechanisms underlying the PSN induced by NRTIs are unclear. In this study, we developed a Drosophila model of NRTI-induced PSN that recapitulates the salient features observed in patients undergoing ART: PSN and nociceptive hypersensitivity. Furthermore, our data demonstrate that pathways known to suppress PSN induced by chemotherapeutic drugs are ineffective in suppressing the PSN or nociception induced by NRTIs. Instead, we found that increased dynamics of a peripheral sensory neuron may possibly underlie NRTI-induced PSN and nociception. Our model provides a solid platform in which to investigate further mechanisms of ART-induced PSN and nociceptive hypersensitivity.This article has an associated First Person interview with the first author of the paper.

Drosophila as a Model for Human Viral Neuroinfections

“…While highly effective at controlling HIV infection, anti-retroviral therapy (ART) is also associated with the development of peripheral sensory neuropathy (PSN) in select patients [ 150 ]. Bush et al demonstrated how ART with AZT (Zidovudine or Azidothymidine) can induce thermal and mechanosensory nociceptive hypersensitivity in larvae [ 218 ]. This sensitization was associated with degeneration in sensory neurons, as measured by an increase in fragmented terminal (distal) dendrites in C4da neurons.…”