Pro-Inflammatory Signaling Upregulates a Neurotoxic Conotoxin-Like Protein Encrypted Within Human Endogenous Retrovirus-K.

Motor neuron degeneration and spinal cord demyelination are hallmark pathological events in Amyotrophic Lateral Sclerosis (ALS). Endogenous retrovirus-K (ERVK) expression has an established association with ALS neuropathology, with murine modeling pointing to a role for the ERVK envelope () gene in disease processes. Here, we describe a novel viral protein cryptically encoded within the ERVK transcript, which resembles two distinct cysteine-rich neurotoxic proteins: conotoxin proteins found in marine snails and the Human Immunodeficiency Virus (HIV) Tat protein.

NF-κB and IRF1 Induce Endogenous Retrovirus K Expression via Interferon-Stimulated Response Elements in Its 5' Long Terminal Repeat.

Unlabelled: Thousands of endogenous retroviruses (ERV), viral fossils of ancient germ line infections, reside within the human genome. Evidence of ERV activity has been observed widely in both health and disease. While this is most often cited as a bystander effect of cell culture or disease states, it is unclear which signals control ERV transcription.

TDP-43 regulates endogenous retrovirus-K viral protein accumulation.

The concomitant expression of neuronal TAR DNA binding protein 43 (TDP-43) and human endogenous retrovirus-K (ERVK) is a hallmark of ALS. Since the involvement of TDP-43 in retrovirus replication remains controversial, we sought to evaluate whether TDP-43 exerts an effect on ERVK expression. In this study, TDP-43 bound the ERVK promoter in the context of inflammation or proteasome inhibition, with no effect on ERVK transcription.