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Human endogenous retrovirus ERVK3-1 characterizes a metabolically active and immunosuppressive subtype of liver

Xiaofen Wen1, Shulv Weng2, Minna Chen1

  • 1Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 515031, Guangdong, China.

Virology Journal
|October 2, 2025
PubMed
Abstract

Insights

Human endogenous retroviruses (HERVs) like ERVK3-1 are linked to liver cancer progression, promoting immune suppression and immunotherapy resistance. Targeting ERVK3-1 may offer new therapeutic strategies for liver hepatocellular carcinoma (LIHC).

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Human endogenous retroviruses (HERVs) are implicated in cancer.
  • The role of ERVK3-1 (HERVK_3p21.31) in liver hepatocellular carcinoma (LIHC) is largely unknown.

Purpose of the Study:

  • Investigate the function of ERVK3-1 in LIHC.
  • Determine ERVK3-1's impact on tumor progression, immune evasion, and immunotherapy response.

Main Methods:

  • Analyzed TCGA-LIHC transcriptomic data for ERVK3-1 expression.
  • Performed functional enrichment, PPI network, and immune analyses.
  • Assessed immunotherapy responsiveness using TIDE and TCIA databases.

Main Results:

  • High ERVK3-1 expression correlates with metabolic and oxidative stress pathways.
  • ERVK3-1 promotes immune suppression and immune checkpoint expression (PD-1, CTLA-4, TIM-3).
  • High ERVK3-1 expression is associated with reduced immunotherapy response and increased immune evasion.

Conclusions:

  • ERVK3-1 contributes to LIHC progression via metabolic reprogramming and immune suppression.
  • ERVK3-1 may serve as a prognostic biomarker and therapeutic target in liver cancer.
  • ERVK3-1 influences tumor microenvironment and resistance to cancer treatments.
Keywords:
ERVK3-1ImmunotherapyLiver hepatocellular carcinomaT-cell exhaustionTumor microenvironment

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