Endogenous retroviruses

Abstract

Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV) sequences, and most represent the remains of ancient germ line infections. Our knowledge of the three distinct classes of ERVs is inversely correlated with their copy number, and their characterization has benefited from the availability of divergent wild mouse species and subspecies, and from ongoing analysis of the Mus genome sequence. In contrast to human ERVs, which are nearly all extinct, active mouse ERVs can still be found in all three ERV classes. The distribution and diversity of ERVs has been shaped by host-virus interactions over the course of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral resistance genes. We review mechanisms by which an adaptive coexistence has evolved. (Part of a Multi-author Review)

MuLV-related endogenous retroviral elements and Flt3 participate in aberrant end-joining events that promote B-cell leukemogenesis

“…In all three fusion genes, the U3 element contained a 190-nt insert found only in polytropic ERVs (Stoye and Coffin 1987). About 40 partial or complete polytropic ERVs are found in most mouse strains, making them the most abundant class of MuLVrelated ERVs (Stocking and Kozak 2008). The ERV/U3 sequence that we identified in TM B-ALL fusion genes perfectly matched 13 ERVs in the mouse genome, including four on chromosome 5 (data not shown).…”

“…It is now appreciated that 4%-10% of vertebrate genomes contain endogenous retrovirus (ERV) sequences, remnants of ancient germline retroviral infections (Stocking and Kozak 2008;Stoye 2012). Class I ERVs, present in 50-100 copies per genome, are closely related to g-retroviruses such as exogenous Moloney leukemia virus (MuLV) with ecotropic, xenotropic, or polytropic host range (Stocking and Kozak 2008;Stoye 2012). Because ERVs are present in high copy number and include repeated sequences, they undergo frequent recombination-based rearrangements that have greatly contributed to remodeling of vertebrate genomes during evolution (Feschotte and Gilbert 2012).…”

The KRAB zinc finger protein ZFP809 is required to initiate epigenetic silencing of endogenous retroviruses

“…However, since MuLV proviruses are absent in most wild Mus species (Stocking and Kozak 2008), we speculated that exogenous and endogenous MuLV are not the only targets of ZFP809. We thus attempted to explore the function of ZFP809 using genome-wide binding analysis and knockout mice.…”

Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis

“…A coordinated B-and T-cell response is a well-established, pivotal defense mechanism against retroviral replication and pathogenesis (24)(25)(26). Innate immunity is also essential to control MuLV, which includes mechanisms that sense the virus and activate adaptive immunity (27), but also mechanisms that inhibit entry or transport to the nucleus, or interfere with reverse transcription accuracy and efficacy (13,28). NSG mice lack cells of the adaptive immune system (B-, T-and NK-cells) and have several defects in classic innate functions, including an absent hemolytic complement system, reduced dendritic cell function, and defective macrophage activity (10).…”

“…As with all mice, the NOD genome contains multiple copies of endogenous retrovirus (ERV) related to the γ-genus of exogenous retrovirus, typified by the family of murine leukemia virus (MuLV) (11,12). The majority of these ERVs are defective because of the irreversible accumulation of mutations; however, this inevitable extinction is counteracted by adaptive mechanisms that work to maintain active ERVs, which are an important source of somatic and genomic diversity (13,14). A good example is the recent and recurrent entry of ecotropic (E)-MuLVs into the Mus musculus germ line, as shown by their insertional polymorphism (15) and evidence of novel insertions in viremic mouse strains (16).…”