Human Endogenous Retrovirus K (HML-2) in Health and Disease

Abstract

Human endogenous retroviruses (HERVs) are derived from exogenous retrovirus infections in the evolution of primates and account for about 8% of the human genome. They were considered as silent passengers within our genomes for a long time, however, reactivation of HERVs has been associated with tumors and autoimmune diseases, especially the HERV-K (HML-2) family, the most recent integration groups with the least number of mutations and the most biologically active to encode functional retroviral proteins and produce retrovirus-like particles. Increasing studies are committed to determining the potential role of HERV-K (HML-2) in pathogenicity. Although there is still no evidence for HERV-K (HML-2) as a direct cause of diseases, aberrant expression profiles of the HERV-K (HML-2) transcripts and their regulatory function to their proximal host-genes were identified in different diseases. In this review, we summarized the advances between HERV-K (HML-2) and diseases to provide basis for further studies on the causal relationship between HERV-K (HML-2) and diseases. We recommended more attention to polymorphic integrated HERV-K (HML-2) loci which could be genetic causative factors and be associated with inter-individual differences in tumorigenesis and autoimmune diseases.

Increased HERV-K(HML-2) Transcript Levels Correlate with Clinical Parameters of Liver Damage in Hepatitis C Patients

“…Thus, they possess the potential to impact the expression of genes and even gene networks in our genome [ 12 , 38 ]. To this end, an increased expression of HERV-K(HML-2) upon HCV infection might result in the expression of viral proteins or changes in host gene expression, contributing to the development of cancers and autoimmune disorders [ 20 , 39 ]. However, further detailed functional analyses need to be performed to clarify the exact functional role of specific HERV-K(HML-2) elements on HCV pathogenesis.…”

“…Some HERV proviruses such as HERV-K(HML-2) express a spliced RNA encoding for proteins such as Rec or NP9 which have been implicated in oncogenesis [ 16 , 17 ]. HERV-K(HML-2) has also been shown to induce neuronal cell death [ 18 , 19 , 20 ] and reverse transcriptase activity could be detected in the cerebrospinal fluid of amyotrophic lateral sclerosis patients [ 21 ]. Additionally, an association between HERV-K(HML-2) and hepatocellular carcinoma (HCC) has been identified [ 22 , 23 ].…”

Implications of Endogenous Retroelements in the Etiopathogenesis of Systemic Lupus Erythematosus

“…New retrotransposon insertions in or near exonic genes can result in altered transcription [ 51 ], disrupted mRNA splicing, premature termination of translation, and loss of protein expression or function. Besides sporadic genetic diseases [ 52 ] caused by new retrotranspositions, this biology is accelerated in malignant cells [ 53 ] and is a major contributor to the activation of oncogenes [ 54 ], the inactivation of tumor suppressors [ 55 , 56 ], and larger chromosomal abnormalities [ 50 , 57 , 58 , 59 ]. Retroelements are also abundant around chromosome fragile sites, such as FRA3B on chromosome 3p14 and FRA16D on chromosome 16q23 [ 60 , 61 ].…”

Human endogenous retroviruses and ageing

“…The majority of human endogenous retroviruses (HERVs) are defective due to the accumulation of mutations and deletions but some proviruses, especially in the youngest families (e.g. HERV-K (HML-2), contain intact genes permitting the production of proviral proteins (for a review, see [1]). The functions of HERVs have been under active investigation for decades and it is now known that far from being quiescent, some are involved in several crucial physiologic processes, clearly advantageous or essential to the host, e.g.…”

“…placentation, neuroprotection and differentiation of cells in early embryos. However, there are now many publications also showing that HERVs are involved in the pathogenesis of several diseases (autoimmune, inflammatory, malignancies) [1].…”