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Abstract
Approximately 10% of the mouse genome is constituted by endogenous retroviruses (ERVs), and a number of mouse ERVs remain active. Many copies of endogenous murine leukemia viruses (MuLVs) are detected in the genomes of inbred mouse strains. Some of these MuLVs are transcriptionally active or produce infectious virus particles. Previously, we identified partial env sequences of new xenotropic MuLVs (X-MuLVs) from a senescence-accelerated mouse (SAM) strain. In the present study, we investigated and characterized the complete sequences of the X-MuLVs. The complete genomes and open reading frames (ORFs) of two X-MuLVs, designated xmlv15 and xmlv18 (accession nos. HQ154630 and HQ154631, respectively), were molecularly cloned from the genome of the SAM mice. We confirmed that the xmlv15 and xmlv18 sequences are distinct from all known MuLV genomes and are most similar to DG-75 MuLV. Moreover, we found that common strains of laboratory mice carry our newly identified xmlvs. Additionally, the expression levels of xmlv15-related sequences were much higher in C57BL and ICR mice than in the SAM strains without any stimulators. Our findings suggest that a specific group of endogenous MuLVs is constitutively expressed in the brain and that they may participate in normal functions and/or pathogenic conditions.
Highlights
10% of the mouse genome is constituted by chromosomally integrated copies of retrovirus sequences referred to as endogenous retroviruses (ERVs) [1]
A phylogenetic analysis constructed with other Murine leukemia viruses (MuLVs) strains based on their full genomes showed that xmlv15 were closely related to xenotropic MuLVs (X-MuLVs), including mouse xenotropic proviruses, DG-75 MuLV, murine type C retrovirus (MTCR) and xenotropic MuLVrelated virus (XMRV) that was isolated from prostate cancer tissue
Through a comparative nucleotide analysis, we confirmed that the sequences of both xmlv15 and xmlv18 are clearly distinct from all known genomes of MuLVs even though they are very closely related to previously reported endogenous X-MuLVs that were found in C57BL/6J mice [21]
Summary
10% of the mouse genome is constituted by chromosomally integrated copies of retrovirus sequences referred to as endogenous retroviruses (ERVs) [1]. These ERV sequences have entered the mouse genome through the spontaneous retroviral infection of germ line cells, and they have been transmitted vertically from one generation to the [2]. MuLVs are categorized as class I ERVs, which are most similar to the gammaretrovirus and are morphologically related to type C retroviruses These sequences include replication-defective or suppressed proviruses and expressed, active ecotropic and xenotropic proviruses [4]. Among MuLVs, certain active MuLV proviruses encoding infectious virions have been suggested to represent etiological cofactors of spontaneous leukemogenesis [13]
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