Abstract
Retroviruses that have the ability to infect germ line cells can become an integral and inherited part of the host genome. About 8% of the human chromosomal DNA consists of sequences derived from infections by retroviruses that presumably circulated 2–40 millions of years ago, and some elements are actually much older. Post-insertional recombinations, deletions, and mutations have rendered all known human endogenous retroviruses (HERVs) non-infectious. However some, particularly the most recently acquired proviruses of the HERV-K(HML-2) family, can expresses viral proteins and produce viral particles. In this review we will first discuss the major aspects of the endogenization process and peculiarities of the different HERV-K families. We will then focus on the genes and proteins encoded by HERV-K(HML-2) as well as inactivation of these proviruses by postinsertional mutations and their inhibition by antiretroviral factors. After describing the evolutionary interplay between host and endogenous retrovirus we will delve deeper into the currently limited understanding of HERV-K and its possible association with disease, particularly tumorigenesis.
Highlights
Human chromosomes contain numerous retroviral sequences that form part of our genetic legacy
Phylogenetic studies have allowed these elements to be sorted into distinct groups that are usually termed “families.” Similar to artifacts in an archeological museum, time has left its traces on these retroviral elements and very often only “shards” of the once complete sequence remain
Not all HML families are described in detail using in silico generated consensus sequences or by analysis of individual elements, a summary of the features of human endogenous retroviruses (HERVs)-K families is given in Table 1, these numbers may need to be revised as was recently done for human mouse mammary tumor virus like-2 (HML-2) solo long terminal repeat (LTR), being adjusted from ∼2500 to 944 [4, 38]
Summary
Human chromosomes contain numerous retroviral sequences that form part of our genetic legacy. In addition to the evidence for the protein-induced or promoted tumorigenesis of somatic cells, HERV-K elements are implicated in cancer development at the DNA or RNA level In this context, HERVK proviruses have been shown to be involved in recombination events that in one setting left an LTR-promoter closely upstream of exons 5–12 of the ETV1 gene that encodes a transcription factor of the Ets family. All HML families belong to the class II/betaretrovirus group, which contain the endogenous and exogenous MMTV, Mason–Pfizer monkey virus (MPMV), and Jaagsiekte sheep retrovirus (JSRV) [31] Elements such as HML-4 and HML-6, which are related to but clearly distinct from the HERV-K(HML-2) prototype virus HERV-K10 [32], were identified more than 20 years ago by extensive lab work using low-stringency Southern blot analyses with MMTVderived gag/pol probes [33]. Not all HML families are described in detail using in silico generated consensus sequences or by analysis of individual elements, a summary of the features of HERV-K families is given in Table 1, these numbers may need to be revised as was recently done for HML-2 solo LTRs, being adjusted from ∼2500 to 944 [4, 38]
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