Human endogenous retrovirus K reverse transcriptase (HERV-K RT)

Human endogenous retrovirus K (HERV-K) reverse transcriptase is a retroviral enzyme encoded by the pol gene of the HERV-K family, specifically the HML-2 subgroup, which is the most transcriptionally active group of endogenous retroviruses in the human genome [1, 17]. Although these viral elements are typically silenced in healthy adults, they can be reactivated in response to environmental triggers or disease states, leading to the production of viral proteins and particles [5, 16]. The reverse transcriptase (RT) functions as an RNA-dependent DNA polymerase, converting viral RNA into cDNA, which can then integrate into the host genome or trigger innate immune signaling pathways [2, 14]. In diseases such as amyotrophic lateral sclerosis (ALS), elevated HERV-K RT activity is associated with neurotoxicity and motor neuron degeneration, while in various cancers, it is linked to tumorigenesis and metastasis [1, 11]. Structurally, HERV-K RT is an asymmetric homodimer that shares significant homology with HIV-1 RT, yet it contains specific amino acid differences that affect its sensitivity to antiretroviral drugs [3, 6]. Current therapeutic approaches involve repurposing HIV-1 nucleoside reverse transcriptase inhibitors (NRTIs), such as abacavir and zidovudine, to suppress HERV-K expression and slow disease progression [8, 13]. However, the development of more potent and selective inhibitors remains a key challenge due to the lower affinity of existing drugs for the HERV-K enzyme compared to their primary HIV-1 target [6, 11].

Other names

HERV-K (HML-2) reverse transcriptaseHK2 RTHuman MMTV-like retrovirus reverse transcriptaseERVK reverse transcriptaseHuman endogenous retrovirus K103 reverse transcriptase

Inhibition of RNA-dependent DNA polymerase activity (reverse transcription)