Journal
RETROVIROLOGY
Volume 15, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12977-018-0416-3
Keywords
-
Categories
Funding
- National Institute of Allergy and Infectious diseases [R3764003]
- UK Medical Research Council [MC_UU_12014/10]
- MRC [MC_UU_12014/10, MC_UU_12014/12] Funding Source: UKRI
Ask authors/readers for more resources
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 similar to 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-a 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available