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Origins of the endogenous and infectious laboratory mouse gammaretroviruses
1. ckozak@niaid.nih.gov.
Abstract:
The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses (XRVs) and as endogenous retroviruses (ERVs) inserted into their host genomes. There are three major mouse leukemia virus (MuLV) subgroups in laboratory mice: ecotropic, xenotropic, and polytropic. These MuLV subgroups differ in host range, pathogenicity, receptor usage and subspecies of origin. The MuLV ERVs are recent acquisitions in the mouse genome as demonstrated by the presence of many full-length nondefective MuLV ERVs that produce XRVs, the segregation of these MuLV subgroups into different house mouse subspecies, and by the positional polymorphism of these loci among inbred strains and individual wild mice. While some ecotropic and xenotropic ERVs can produce XRVs directly, others, especially the pathogenic polytropic ERVs, do so only after recombinations that can involve all three ERV subgroups. Here, I describe individual MuLV ERVs found in the laboratory mice, their origins and geographic distribution in wild mouse subspecies, their varying ability to produce infectious virus and the biological consequences of this expression.
Insights
Mouse leukemia viruses (MuLVs) exist as exogenous viruses (XRVs) and endogenous retroviruses (ERVs) in mice. These retroviruses, with distinct subgroups, show recent genomic integration and varying infectious potential, influencing leukemogenesis.
Area of Science:
- Virology
- Genomics
- Mouse Models
Background:
- Mouse leukemia viruses (MuLVs) are gammaretroviruses linked to leukemogenesis.
- These viruses exist as exogenous viruses (XRVs) and endogenous retroviruses (ERVs) in mouse genomes.
- Three major MuLV subgroups (ecotropic, xenotropic, polytropic) exhibit distinct characteristics.
Purpose of the Study:
- To describe individual MuLV ERVs in laboratory mice.
- To investigate their origins, geographic distribution, and infectious potential.
- To understand the biological consequences of MuLV ERV expression.
Main Methods:
- Analysis of MuLV ERV sequences and genomic integration.
- Subspecies distribution studies in wild mice.
- Assessment of infectious virus production and recombination events.
Main Results:
- MuLV ERVs are recent genomic acquisitions with significant positional polymorphism.
- Some ERVs directly produce XRVs, while others require recombination.
- Polytropic ERVs are particularly associated with pathogenic recombinations.
Conclusions:
- MuLV ERVs exhibit diverse origins and geographic spread across mouse subspecies.
- Their varying capacity to produce infectious virus and undergo recombination impacts host health.
- Understanding MuLV ERVs is crucial for studying leukemogenesis in mice.
