Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

Area of Science:

• Genomics
• Molecular Biology
• Virology

Background:

• The human genome harbors numerous human endogenous retroviruses (HERVs), remnants of ancient retroviral integrations.
• Initially regarded as inactive 'junk' DNA due to silencing mechanisms like methylation and heterochromatin localization.
• Emerging evidence highlights their active role in regulating gene expression across various physiological and pathological states.

Purpose of the Study:

• To review factors influencing human endogenous retrovirus (HERV) activity.
• To present evidence of gene regulatory functions of HERV long terminal repeats (LTRs) in diverse model organisms.
• To discuss molecular pathways through which HERVs impact cellular and physiological events.

Main Methods:

• Literature review of studies on HERV activity and gene regulation.
• Analysis of evidence from model organisms (mice, rats, zebrafish, worms, flies) demonstrating HERV LTR function.
• Synthesis of information on molecular and cellular pathways modulated by HERVs.

Main Results:

• HERVs are activated in conditions like COVID-19, indicating their relevance in current health challenges.
• HERV LTRs exhibit gene regulatory activity across multiple model systems.
• HERVs influence epigenetic modifications, calcium signaling, protein phosphorylation, and cytokine release via specific pathways.

Conclusions:

• Human endogenous retroviruses (HERVs) are not inert genomic relics but active regulators of gene expression.
• Understanding HERV involvement in disease pathogenesis is crucial for developing targeted therapeutic strategies.
• Further research into HERV functions can unlock novel approaches for treating diseases.