Mammalian Endogenous Retroviruses

Abstract

Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles.

A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer

“…Notably, the average number of LTR-promoted transcripts is significantly higher in the cancer samples, possibly indicating widespread de-repression of LTRs in colon cancer. This trend holds for all major classes of human ERVs, namely LTRs of the ERV1, ERVL and MaLR classes, with the latter two being generally older than ERV1 elements [87, 92] (Fig 1B and S1B Fig). …”

“…Fig 1A and S1A Fig show that for both the cancer and normal samples, LTR-promoted chimeric transcripts are over-represented and LINE and SINE promoted chimeric transcripts are underrepresented based on genomic abundance. Such a result is expected since the vast majority of ERV/LTR related sequences in the genome are in the form of solitary LTRs, which naturally contain promoters [18, 86, 87]. In contrast, most LINE-related sequences in the genome are 5’ truncated, lacking the promoter [88, 89], and SINE sequences such as Alu elements contain PolIII promoters, which are weak and position dependent [90, 91].…”

How Active Are Porcine Endogenous Retroviruses (PERVs)?

“…Endogenous retroviruses are the result of an infection of germ cells with a retrovirus leading to the integration of the viral genome as DNA copy (provirus) in all cells of the organism [1,2,3]. Human endogenous retroviruses (HERVs), especially HERV-K, are well characterised and it has been shown that most of them are defective: if they are expressed in human tumour cells, they are rarely released as particles and even if they are not defective then they are not infectious [4].…”

Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases

“…While human DNA transposons are no longer transposition-competent due to inactivating mutations (Lander et al 2001;Pace 2nd and Feschotte 2007), long interspersed element-1 (LINE-1 or L1) retrotransposons are the only autonomously active family of TEs in humans and form 17% of our genome (Richardson et al 2015). LINE-1s and the non-autonomous short interspersed element-1 (SINEs, such as human Alu elements) are members of the non-long terminal repeat (LTR) class of retrotransposons (Richardson et al 2015), while human endogenous retroviruses (ERVs) belong to the LTR class (Stocking and Kozak 2008;Stoye 2012;Mager and Stoye 2015). The majority of LINE-1 elements in the human genome are inactive fossils due to 5' truncation, internal rearrangements, and point mutations (Lander et al 2001;Khan et al 2006).…”