scholarly journals Xenotropic Mouse Gammaretroviruses Isolated from Pre-Leukemic Tissues Include a Recombinant

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 418 ◽  
Author(s):  
Devinka Bamunusinghe ◽  
Matthew Skorski ◽  
Alicia Buckler-White ◽  
Christine Kozak
Keyword(s):  
Long Terminal Repeat ◽  
Host Range ◽  
Reference Genome ◽  
Endogenous Retroviruses ◽  
Mouse Leukemia ◽  
Naturally Occurring ◽  
C Terminus ◽  
Pathogenic Viruses ◽  
Leukemia Viruses ◽  
Akr Mice

Naturally-occurring lymphomagenesis is induced by mouse leukemia viruses (MLVs) carried as endogenous retroviruses (ERVs). Replicating the ecotropic MLVs recombines with polytropic (P-ERVs) and xenotropic ERVs (X-ERVs) to generate pathogenic viruses with an altered host range. While most recovered nonecotropic recombinants have a polytropic host range, the X-MLVs are also present in the pre-leukemic tissues. We analyzed two such isolates from the AKR mice to identify their ERV progenitors and to look for evidence of recombination. AKR40 resembles the active X-ERV Bxv1, while AKR6 has a Bxv1-like backbone with substitutions that alter the long terminal repeat (LTR) enhancer and the envelope (env). AKR6 has a modified xenotropic host range, and its Env residue changes all lie outside of the domain that governs the receptor choice. The AKR6 segment spanning the two substitutions, but not the entire AKR6 env-LTR, exists as an ERV, termed Xmv67, in AKR, but not in the C57BL/6 mice. This suggests that AKR6 is the product of one, not two, recombination events. Xmv67 originated in the Asian mice. These data indicate that the recombinant X-MLVs that can be generated during lymphomagenesis, describe a novel X-ERV subtype found in the AKR genome, but not in the C57BL/6 reference genome, and identify residues in the envelope C-terminus that may influence the host range.

scholarly journals Recombinant Origins of Pathogenic and Nonpathogenic Mouse Gammaretroviruses with Polytropic Host Range

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Devinka Bamunusinghe ◽  
Qingping Liu ◽  
Ronald Plishka ◽  
Michael A. Dolan ◽  
Matthew Skorski ◽  
...  
Keyword(s):  
Host Range ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Long Terminal Repeats ◽  
Pathogenic Potential ◽  
Mouse Leukemia ◽  
Naturally Occurring ◽  
N Terminus ◽  
Terminal Repeats ◽  
Leukemia Viruses

ABSTRACT Ecotropic, xenotropic, and polytropic mouse leukemia viruses (E-, X-, and P-MLVs) exist in mice as infectious viruses and endogenous retroviruses (ERVs) inserted into mouse chromosomes. All three MLV subgroups are linked to leukemogenesis, which involves generation of recombinants with polytropic host range. Although P-MLVs are deemed to be the proximal agents of disease induction, few biologically characterized infectious P-MLVs have been sequenced for comparative analysis. We analyzed the complete genomes of 16 naturally occurring infectious P-MLVs, 12 of which were typed for pathogenic potential. We sought to identify ERV progenitors, recombinational hot spots, and segments that are always replaced, never replaced, or linked to pathogenesis or host range. Each P-MLV has an E-MLV backbone with P- or X-ERV replacements that together cover 100% of the recombinant genomes, with different substitution patterns for X- and P-ERVs. Two segments are always replaced, both coding for envelope (Env) protein segments: the N terminus of the surface subunit and the cytoplasmic tail R peptide. Viral gag gene replacements are influenced by host restriction genes Fv1 and Apobec3. Pathogenic potential maps to the env transmembrane subunit segment encoding the N-heptad repeat (HR1). Molecular dynamics simulations identified three novel interdomain salt bridges in the lymphomagenic virus HR1 that could affect structural stability, entry or sensitivity to host immune responses. The long terminal repeats of lymphomagenic P-MLVs are differentially altered by recombinations, duplications, or mutations. This analysis of the naturally occurring, sometimes pathogenic P-MLV recombinants defines the limits and extent of intersubgroup recombination and identifies specific sequence changes linked to pathogenesis and host interactions. IMPORTANCE During virus-induced leukemogenesis, ecotropic mouse leukemia viruses (MLVs) recombine with nonecotropic endogenous retroviruses (ERVs) to produce polytropic MLVs (P-MLVs). Analysis of 16 P-MLV genomes identified two segments consistently replaced: one at the envelope N terminus that alters receptor choice and one in the R peptide at the envelope C terminus, which is removed during virus assembly. Genome-wide analysis shows that nonecotropic replacements in the progenitor ecotropic MLV genome are more extensive than previously appreciated, covering 100% of the genome; contributions from xenotropic and polytropic ERVs differentially alter the regions responsible for receptor determination or subject to APOBEC3 and Fv1 restriction. All pathogenic viruses had modifications in the regulatory elements in their long terminal repeats and differed in a helical segment of envelope involved in entry and targeted by the host immune system. Virus-induced leukemogenesis thus involves generation of complex recombinants, and specific replacements are linked to pathogenesis and host restrictions.

Properties of mouse leukemia viruses XVI. Suppression of spontaneous fatal leukemias in AKR mice by treatment with broadly reacting antibody against the viral glycoprotein gp 71

Virology ◽  
1979 ◽  
Vol 93 (1) ◽  
pp. 159-174 ◽  
Author(s):  
Heinz Schwarz ◽  
Peter J. Fischinger ◽  
James N. Ihle ◽  
Heinz-Jorgen Thiel ◽  
Frank Weiland ◽  
...  
Keyword(s):  
Viral Glycoprotein ◽  
Mouse Leukemia ◽  
Leukemia Viruses ◽  
Akr Mice

scholarly journals Amphotropic host range of naturally occuring wild mouse leukemia viruses.

1976 ◽  
Vol 19 (1) ◽  
pp. 13-18 ◽  
Author(s):  
S Rasheed ◽  
M B Gardner ◽  
E Chan
Keyword(s):  
Host Range ◽  
Wild Mouse ◽  
Mouse Leukemia ◽  
Leukemia Viruses

scholarly journals Naturally Occurring Polymorphisms of the Mouse Gammaretrovirus Receptors CAT-1 and XPR1 Alter Virus Tropism and Pathogenicity

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Christine A. Kozak
Keyword(s):  
Host Range ◽  
Binding Sites ◽  
Mammalian Species ◽  
Endogenous Retroviruses ◽  
Laboratory Mice ◽  
Virus Binding ◽  
Virus Envelope ◽  
Naturally Occurring ◽  
Mouse Cells ◽  
Genetic Conflicts

Gammaretroviruses of several different host range subgroups have been isolated from laboratory mice. The ecotropic viruses infect mouse cells and rely on the host CAT-1 receptor. The xenotropic/polytropic viruses, and the related human-derived XMRV, can infect cells of other mammalian species and use the XPR1 receptor for entry. The coevolution of these viruses and their receptors in infected mouse populations provides a good example of how genetic conflicts can drive diversifying selection. Genetic and epigenetic variations in the virus envelope glycoproteins can result in altered host range and pathogenicity, and changes in the virus binding sites of the receptors are responsible for host restrictions that reduce virus entry or block it altogether. These battleground regions are marked by mutational changes that have produced 2 functionally distinct variants of the CAT-1 receptor and 5 variants of the XPR1 receptor in mice, as well as a diverse set of infectious viruses, and several endogenous retroviruses coopted by the host to interfere with entry.

scholarly journals Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice

2016 ◽  
Vol 90 (8) ◽  
pp. 4186-4198 ◽  
Author(s):  
Devinka Bamunusinghe ◽  
Zohreh Naghashfar ◽  
Alicia Buckler-White ◽  
Ronald Plishka ◽  
Surendranath Baliji ◽  
...  
Keyword(s):  
Host Range ◽  
Y Chromosome ◽  
House Mouse ◽  
Laboratory Mouse ◽  
Wild Mouse ◽  
Sequence Diversity ◽  
Laboratory Mice ◽  
Wild Mice ◽  
Mouse Leukemia ◽  
Leukemia Viruses

ABSTRACTMouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus. Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region ofenv. Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents.IMPORTANCELaboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution.

Characterization of Purely Ecotropic and Amphotropic Naturally Occurring Wild Mouse Leukemia Viruses

Intervirology ◽  
1977 ◽  
Vol 8 (6) ◽  
pp. 323-335 ◽  
Author(s):  
Suraiya Rasheed ◽  
Eva Toth ◽  
Murray B. Gardner
Keyword(s):  
Wild Mouse ◽  
Mouse Leukemia ◽  
Naturally Occurring ◽  
Leukemia Viruses

Genetic evidence for a product of the Fv-1 locus that transfers resistance to mouse leukemia viruses.

1976 ◽  
Vol 20 (3) ◽  
pp. 589-596 ◽  
Author(s):  
R W Tennant ◽  
B Schluter ◽  
F E Myer ◽  
J A Otten ◽  
W K Yang ◽  
...  
Keyword(s):  
Genetic Evidence ◽  
Mouse Leukemia ◽  
Leukemia Viruses
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