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Retrovirology. 2018 May 2;15(1):34. doi: 10.1186/s12977-018-0416-3.

Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L.

Author information

1
Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
4
Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. pbieniasz@rockefeller.edu.

Abstract

BACKGROUND:

About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos. However, MuERV-L sequences present in modern mouse genomes have not been observed to replicate.

RESULTS:

Here, we describe the reconstruction of an ancestral MuERV-L (ancML) sequence through paleovirological analyses of MuERV-L elements in the modern mouse genome. The resulting MuERV-L (ancML) sequence was synthesized and a reporter gene embedded. The reconstructed MuERV-L (ancML) could replicate in a manner that is dependent on reverse transcription and generated de novo integrants. Notably, MuERV-L (ancML) exhibited a narrow host range. Interferon-α could reduce MuERV-L (ancML) replication, suggesting the existence of interferon-inducible genes that could inhibit MuERV-L replication. While mouse APOBEC3 was able to restrict the replication of MuERV-L (ancML), inspection of endogenous MuERV-L sequences suggested that the impact of APOBEC3 mediated hypermutation on MuERV-L has been minimal.

CONCLUSION:

The reconstruction of an ancestral MuERV-L sequence highlights the potential for the retroviral fossil record to illuminate ancient events and enable studies of the impact of retroviral elements on animal evolution.

PMID:
29716624
PMCID:
PMC5930517
DOI:
10.1186/s12977-018-0416-3
[Indexed for MEDLINE]
Free PMC Article

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