Human Endogenous Retrovirus-K and TDP-43 Expression Bridges ALS and HIV Neuropathology

Front Microbiol. 2017 Oct 11:8:1986. doi: 10.3389/fmicb.2017.01986. eCollection 2017.


Despite the repetitive association of endogenous retroviruses in human disease, the mechanisms behind their pathological contributions remain to be resolved. Here we discuss how neuronal human endogenous retrovirus-K (HERV-K) expression in human immunodeficiency virus (HIV)-infected individuals is a distinct pathological aspect of HIV-associated neurological conditions, such as HIV encephalitis and HIV-associated neurocognitive disorders. Enhanced neuronal HERV-K levels were observed in the majority of HIV-infected individuals, and to a higher degree in brain tissue marked by HIV replication. Moreover, we highlight an important neuropathological overlap between amyotrophic lateral sclerosis and HIV encephalitis, that being the formation of neurotoxic TDP-43 deposits in neurons. Herein, we argue for enhanced transdisciplinary research in the field of ERV biology, using an example of how HERV-K expression has novel mechanistic and therapeutic implications for HIV neuropathology.

Keywords: NeuroAIDS; TDP-43; amyotrophic lateral sclerosis (ALS); human endogenous retrovirus-K (HERV-K); human immunodeficiency virus (HIV).