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

Blanco-Melo, D., Gifford, R. J. and Bieniasz, P. D. (2018) Reconstruction of a replication-competent ancestral murine endogenous retrovirus-L. Retrovirology, 15, 34. (doi:10.1186/s12977-018-0416-3) (PMID:29716624) (PMCID:PMC5930517)

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Abstract

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. 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. 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.

Item Type:Articles
Additional Information:This work was supported by a grant from the National Institute of Allergy and Infectious diseases (R3764003 to PDB) and a grant from the UK Medical Research Council (MC_UU_12014/10 to RJG).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gifford, Dr Robert
Authors: Blanco-Melo, D., Gifford, R. J., and Bieniasz, P. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Retrovirology
Publisher:BioMed Central
ISSN:1742-4690
ISSN (Online):1742-4690
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Retrovirology 15:34
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
UNSPECIFIEDUNSPECIFIEDUNSPECIFIEDUNSPECIFIEDUNSPECIFIEDUNSPECIFIEDMVLS III - CENTRE FOR VIRUS RESEARCH