Human endogenous retrovirus K (HERV-K)

Human endogenous retrovirus K (HERV-K), particularly the HML-2 clade, is a family of retroviral elements that integrated into the human germline millions of years ago and now constitutes approximately 8% of the human genome [2, 11]. Unlike most other endogenous retroviruses, HERV-K has retained relatively intact open reading frames, allowing it to produce functional viral proteins including Envelope (Env), Gag, and Reverse Transcriptase [3, 6]. While typically silenced in adult somatic tissues, HERV-K is reactivated in several diseases, most notably in cancers such as melanoma, breast, and prostate cancer, and in neurodegenerative conditions like amyotrophic lateral sclerosis (ALS) [1, 4, 10]. The HERV-K Env protein is of particular interest as a therapeutic target due to its role in promoting cell-cell fusion, neurotoxicity, and immune suppression [3, 6, 12]. Current therapeutic approaches include the use of nucleoside reverse transcriptase inhibitors (NRTIs) and integrase inhibitors originally developed for HIV-1, as well as emerging immunotherapies like monoclonal antibodies and CAR-T cells [5, 7, 10, 14]. These interventions aim to suppress viral protein production or eliminate cells expressing HERV-K antigens to mitigate disease progression [1, 13].

Other names

HERV-K (HML-2)Human teratocarcinoma-derived virusHDTVERVKClass II endogenous retrovirusHLM-2HML-2HERV-K10

Reverse transcriptase inhibition, Integrase inhibition, Envelope protein neutralization, Antigen-specific immune activation