Roles of Human Endogenous Retrovirus-K-Encoded Np9 in Human Diseases: A Small Protein with Big Functions

Abstract

Human Endogenous Retrovirus Sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a small protein translated from the HERV-K env reading frame, has been reported as an oncogenic protein and is present in a variety of tumors and transformed cells. The Np9 protein can crosstalk with many cellular factors and is involved in the pathogenicity of various diseases, including some oncogenic virus infections. In the current review, we summarize recent findings about Np9 clinical relevance/implications, its mediated cellular functions/mechanisms, and potential targeted therapies in development.

Keywords: HERV-K; Np9; human diseases; retrovirus; treatment.

Figure 1

Different types of proviral transcripts of HERV-K (HML-2). The HERV-K (HML-2) usually expresses a full-length transcript (8.6 kb) and encodes the Gag, Pro, Pol and Env polyproteins. Env gene transcripts two singly spliced products, a 3.3-kb product to encode Env polyprotein, and a 1.5 kb product of unknown function known as the hel transcript, and a doubly spliced product (1.8 kb) to encode either the Rec or Np9 accessory proteins depending on the presence or absence of a 292-bp deletion at the pol/env boundary.

Figure 2

Schematic diagram of potential mechanisms for activation of Np9 protein promoting KSHV-induced tumorigenesis. AIG: anchorage-independent growth; DDR: DNA damage response.