HERV-K Modulates the Immune Response in ALS Patients

Abstract

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.

Immunogenicity of the Envelope Surface Unit of Human Endogenous Retrovirus K18 in Mice

“…To bridge the gap from a general immunogenic effect of HERV-K18 to a possible involvement in autoimmune diseases, as discussed in the literature [ 27 , 28 , 45 , 46 ], we used the EAE model. Previous work from H. Perron and colleagues [ 39 ] showed that the full-length and surface units of HERV-W were able to trigger EAE-like symptoms in mice if they were administered instead of mycobacteria.…”

Bridging the Gap Between Environmental Adversity and Neuropsychiatric Disorders: The Role of Transposable Elements

“…Additionally, one recent study found simulation of lymphocytes with a HERV-K env peptide significantly upregulated expression of IL-6 in patients with amyotrophic lateral sclerosis (ALS) but not in healthy controls ( Arru et al, 2021 ). It has been hypothesized that cytokines may be similiarly elicited in the brain following aberrant HERV insertions within certain regions, especially hippocampus and amygdala, after exposure to stress or infection.…”

Identification and characterization of the HERV-K (HML-8) group of human endogenous retroviruses in the genome

“…Several proteins encoded by HERV-K are related to cancer, such as germ cell tumors, teratocarcinoma, ovarian cancer, prostate cancer, melanoma, rheumatoid arthritis, and amyotrophic lateral sclerosis (Mameli et al 2017;Arru et al 2018;Garcia-Montojo et al 2018;Arru et al 2021). Np9 promotes the growth of myeloid and lymphoblastic leukemia cells by activation of Notch1, ERK, and AKT pathways through upregulation of β-catenin (Chen et al 2013).…”