Endogenous Retroviral Types and Distribution

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Human endogenous retroviruses (HERVs) are a family of human Long Terminal Repeat retrotransposons that resemble simple retroviruses in structure. HERVs and the related non-autonomous mammalian apparent LTR- retrotransposon (MaLRs) comprise ~8% of genomic DNA. A single letter is used to denote the tRNA primer used to initiate HERV reverse transcription (e.g. HERV-K elements initiate cDNA synthesis using a lysine tRNA).
Most HERVs retrotransposed in the distant past, are replication-defective, and are fixed in the population. However, some HERV-K elements are polymorphic in humans. One element, HERV-K113, has intact open reading frames and can produce viral particles in vitro. Moreover, the Heidmann and Bieniasz groups have reanimated replication-competent HERV-K elements from in silico derived consensus sequences.

HERV-Ks are expressed in certain tumors, and some have suggested that HERV expression may play a role in the etiology of some cancers as well as certain neurological and autoimmune diseases. However, this remains somewhat controversial and the jury is out on the following questions: 1) Are any functional HERV-K elements present in humans? 2) Can partially functional HERV-K elements complement each other in trans to produce functional virions? 3) Is HERV activity associated with disease?

Eichler and colleagues found that the chimpanzee and gorilla genomes were bombarded by independent endogenous retrovirus (ERV) infections approximately 3-4 MYa. These data suggest that the gorilla and chimpanzee may still harbor active ERVs and that these genomes be more permissive for endogenous retrovirus infections when compared to humans.

HERV-derived sequences also can be co-opted by the host. For example, the human syncytin gene appears to be derived from the HERV-W envelope gene and may function in placental morphogenesis. Similarly, the paternally expressed Peg10 gene appears to be derived from the gag and protease domains of an ancient Ty3/gypsy LTR retrotransposon and is critical for placental development. Thus, LTR-retrotransposons have impacted mammalian genomes in various ways.


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