Genetic basis for resistance to polytropic murine leukemia viruses in the wild mouse species Mus castaneus.

ABSTRACT Virtually all of our present understanding of endogenous murine leukemia viruses (MLVs) is based on studies with inbred mice. To develop a better understanding of the interaction between endogenous retroviruses and their hosts, we have carried out a systematic investigation of endogenous nonecotropic MLVs in wild mice. Species studied included four major subspecies of Mus musculus(M. m. castaneus, M. m. musculus, M. m. molossinus, and M. m. domesticus) as well as four common inbred laboratory strains (AKR/J, HRS/J, C3H/HeJ, and C57BL/6J). We determined the detailed distribution of nonecotropic proviruses in the mice by using both env- and long terminal repeat (LTR)-derived oligonucleotide probes specific for the three different groups of endogenous MLVs. The analysis indicated that proviruses that react with all of the specific probes are present in most wild mouse DNAs tested, in numbers varying from 1 or 2 to more than 50. Although in common inbred laboratory strains the linkage of group-specific sequences in env and the LTR of the proviruses is strict, proviruses which combine env and the LTR sequences from different groups were commonly observed in the wild-mouse subspecies. The “recombinant” nonecotropic proviruses in the mouse genomes were amplified by PCR, and their genetic and recombinant natures were determined. These proviruses showed extended genetic variation and provide a valuable probe for study of the evolutionary relationship between MLVs and the murine hosts.

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Virological Properties and Nucleotide Sequences of Cas-E-Type Endogenous Ecotropic Murine Leukemia Viruses in South Asian Wild Mice, Mus musculus castaneus

Journal of Virology ◽

10.1128/jvi.75.11.5049-5058.2001 ◽

2001 ◽

Vol 75 (11) ◽

pp. 5049-5058 ◽

Cited By ~ 12

Author(s):

Hidetoshi Ikeda ◽

Kanako Kato ◽

Hiroshi Kitani ◽

Takako Suzuki ◽

Takamasa Yoshida ◽

...

Keyword(s):

Mus Musculus ◽

Antigenic Variation ◽

Wild Mouse ◽

Wild Mice ◽

Multiple Copies ◽

Restricted Region ◽

Genomic Dnas ◽

Spontaneous Expression ◽

Leukemia Viruses ◽

Murine Leukemia

ABSTRACT Two types of endogenous ecotropic murine leukemia viruses (MuLVs), termed AKV- and Cas-E-type MuLVs, differ in nucleotide sequence and distribution in wild mouse subspecies. In contrast to AKV-type MuLV, Cas-E-type MuLV is not carried by common laboratory mice. Wild mice ofMus musculus (M. m.) castaneus carry multiple copies of Cas-E-type endogenous MuLV, including the Fv-4r gene that is a truncated form of integrated MuLV and functions as a host's resistance gene against ecotropic MuLV infection. Our genetic cross experiments showed that only the Fv-4r gene was associated with resistance to ecotropic F-MuLV infection. Because the spontaneous expression of infectious virus was not detected in M. m. castaneus, we generated mice that did not carry the Fv-4r gene but did carry a single or a few endogenous MuLV loci. In mice not carrying theFv-4r gene, infectious MuLVs were isolated in association with three of six Cas-E-type endogenous MuLV loci. The isolated viruses showed a weak syncytium-forming activity for XC cells, an interfering property of ecotropic MuLV, and a slight antigenic variation. Two genomic DNAs containing endogenous Cas-E-type MuLV were cloned and partially sequenced. All of the Cas-E-type endogenous MuLVs were closely related, hybrid-type viruses with an ecotropicenv gene and a xenotropic long terminal repeat. Duplications and a deletion were found in a restricted region of the hypervariable proline-rich region of Env glycoprotein.

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Cell-surface antigens associated with recombinant mink cell focus-inducing murine leukemia viruses.

Journal of Experimental Medicine ◽

10.1084/jem.149.3.702 ◽

1979 ◽

Vol 149 (3) ◽

pp. 702-712 ◽

Cited By ~ 30

Author(s):

M W Cloyd ◽

J W Hartley ◽

W P Rowe

Keyword(s):

Cell Surface ◽

High Titer ◽

Wild Mouse ◽

Antigenic Determinants ◽

Cell Surface Antigens ◽

Xenotropic Murine Leukemia ◽

Naturally Occurring ◽

Mink Cell ◽

Leukemia Viruses ◽

Murine Leukemia

Distinct type-specific antigens were detected on cells infected with cloned mink cell focus-inducing (MCF) murine leukemia viruses by means of cell surface immunofluorescence absorption assays with rabbit antisera raised against naturally-occurring AKR MCF viruses. The MCF type-specific antibodies were present in high titer and not absorbable by cells infected with ecotropic, xenotropic, or wild mouse amphotropic murine leukemia viruses, or combinations of ecotropic and xenotropic viruses. Three MCF subtype-specific reactions were identified. One subspecificity (operationally designated MCFA-1) defined antigenic determinant(s) distributed among MCF viruses in general. Another (MCFA-2) specified determinant(s) induced by all naturally occurring MCF isolates not of Friend or Moloney origin. A third subspecificity (MCFA-3) was induced by some MCF isolates, and not by others; the presence of this antigen did not correlate with the source of any presently known biological property of the viruses. In addition, type-specific antigenic determinants of ecotropic and xenotropic murine leukemia viruses were expressed on MCF virus-infected cells. The serological profile of MCF viruses thus supports the contention that they are env gene recombinants between ecotropic and xenotropic murine leukemia viruses. However, new, distinct MCF-specific determinants are also generated, and these could be useful markers in studying MCF viruses.

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Wild Mouse Variants of Envelope Genes of Xenotropic/Polytropic Mouse Gammaretroviruses and Their XPR1 Receptors Elucidate Receptor Determinants of Virus Entry

Journal of Virology ◽

10.1128/jvi.00933-07 ◽

2007 ◽

Vol 81 (19) ◽

pp. 10550-10557 ◽

Cited By ~ 29

Author(s):

Yuhe Yan ◽

Ryan C. Knoper ◽

Christine A. Kozak

Keyword(s):

Virus Entry ◽

Wild Mouse ◽

Receptor Site ◽

Viral Envelope ◽

Amino Acid Residues ◽

Identify Amino Acid ◽

Mouse Species ◽

Mouse Cells ◽

Leukemia Viruses ◽

Nih 3T3

ABSTRACT Mouse xenotropic and polytropic leukemia viruses (XMVs and PMVs) are closely related gammaretroviruses that use the XPR1 receptor for entry. To identify amino acid residues in XPR1 important for virus entry, we tested mouse cells derived from evolutionarily divergent species for susceptibility to prototypical PMVs, XMVs, and the wild mouse isolate CasE#1. CasE#1 has a variant XMV/PMV host range, and sequence analysis of the CasE#1 env gene identifies segments related to PMVs and XMVs. Cells from the Asian mouse species Mus pahari show a unique pattern of susceptibility to these three viruses; these cells are susceptible to XMVs and CasE#1 but are resistant to PMVs, whereas NIH 3T3 cells show the reciprocal pattern, susceptibility to only PMVs. The M. pahari XPR1 gene differs from that of NIH 3T3 in the two extracellular loops (ECLs) previously shown to mediate virus entry (M. Marin, C. S. Tailor, A. Nouri, S. L. Kozak, and D. Kabat, J. Virol. 73:9362-9368, 1999, and N. S. Van Hoeven and A. D. Miller, Retrovirology 2:76, 2005). Using transfected hamster cells expressing chimeric and mutated XPR1s, we demonstrated that the susceptibility differences between NIH 3T3 and M. pahari cells are receptor mediated, that PMV entry requires residues in ECL3, that the CasE#1 entry determinant is in ECL4, and that determinants for XMV entry are in both ECL3 and ECL4. Additional substitutions in ECL3 and ECL4 modulate virus susceptibility and suggest that ECL3 and ECL4 may contribute to the formation of a single virus receptor site. The position of M. pahari at the base of the Mus phylogenetic tree indicates that XPR1-mediated susceptibility to XMVs is the ancestral type in this genus and that the phenotypic variants of mouse XPR1 likely arose in conjunction with exposure to gammaretrovirus infections and coevolutionary adaptations in the viral envelope.

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Acquisition of two endogenous ecotropic murine leukemia viruses in distinct Asian wild mouse populations.

Journal of Virology ◽

10.1128/jvi.65.4.1796-1802.1991 ◽

1991 ◽

Vol 65 (4) ◽

pp. 1796-1802 ◽

Cited By ~ 15

Author(s):

Y Inaguma ◽

N Miyashita ◽

K Moriwaki ◽

W C Huai ◽

M L Jin ◽

...

Keyword(s):

Wild Mouse ◽

Leukemia Viruses ◽

Murine Leukemia

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Characterization of Recombinant Nonecotropic Murine Leukemia Viruses from the Wild Mouse Species Mus spretus

Journal of Virology ◽

10.1128/jvi.77.23.12773-12781.2003 ◽

2003 ◽

Vol 77 (23) ◽

pp. 12773-12781 ◽

Cited By ~ 11

Author(s):

Yong Tae Jung ◽

Tiyun Wu ◽

Christine A. Kozak

Keyword(s):

Germ Line ◽

Laboratory Mouse ◽

Wild Mouse ◽

Recombination Breakpoint ◽

Rnase H ◽

Functional Genes ◽

Mus Spretus ◽

Mouse Species ◽

Leukemia Viruses

ABSTRACT The wild mouse species most closely related to the common laboratory strains contain proviral env genes of the xenotropic/polytropic subgroup of mouse leukemia viruses (MLVs). To determine if the polytropic proviruses of Mus spretus contain functional genes, we inoculated neonates with Moloney MLV (MoMLV) or amphotropic MLV (A-MLV) and screened for viral recombinants with altered host ranges. Thymus and spleen cells from MoMLV-inoculated mice were plated on Mus dunni cells and mink cells, since these cells do not support the replication of MoMLV, and cells from A-MLV-inoculated mice were plated on ferret cells. All MoMLV-inoculated mice produced ecotropic viruses that resembled their MoMLV progenitor, although some isolates, unlike MoMLV, grew to high titers in M. dunni cells. All of the MoMLV-inoculated mice also produced nonecotropic virus that was infectious for mink cells. Sequencing of three MoMLV- and two A-MLV-derived nonecotropic recombinants confirmed that these viruses contained substantial substitutions that included the regions of env encoding the surface (SU) protein and the 5′ end of the transmembrane (TM) protein. The 5′ recombination breakpoint for one of the A-MLV recombinants was identified in RNase H. The M. spretus-derived env substitutions were nearly identical to the corresponding regions in prototypical laboratory mouse polytropic proviruses, but the wild mouse infectious viruses had a more restricted host range. The M. spretus proviruses contributing to these recombinants were also sequenced. The seven sequenced proviruses were 99% identical to one another and to the recombinants; only two of the seven had obvious fatal defects. We conclude that the M. spretus proviruses are likely to be recent germ line acquisitions and that they contain functional genes that can contribute to the production of replication-competent virus.

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Recent Studies on a Murine Leukemia Virus Grown in Tissue Culture

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060544 ◽

1967 ◽

Vol 25 ◽

pp. 106-107

Author(s):

L. Z. de Tkaczevski ◽

E. de Harven ◽

C. Friend

Keyword(s):

Tissue Culture ◽

Solid Tumors ◽

Murine Leukemia Virus ◽

Leukemia Virus ◽

Supernatant Fluid ◽

Virus Particles ◽

Friend Leukemia ◽

Type C ◽

Leukemia Viruses ◽

Murine Leukemia

Despite extensive studies, the correlation between the morphology and pathogenicity of murine leukemia viruses (MLV) has not yet been clarified. The virus particles found in the plasma of leukemic mice belong to 2 distinct groups, 1 or 2% of them being enveloped A particles and the vast majority being of type C. It is generally believed that these 2 types of particles represent different phases in the development of the same virus. Particles of type A have been thought to be an earlier form of type C particles. One of the tissue culture lines established from Friend leukemia solid tumors has provided the material for the present study. The supernatant fluid of the line designated C-1A contains an almost pure population of A particles as illustrated in Figure 1. The ratio is, therefore, the reverse of what is unvariably observed in the plasma of leukemic mice where C particles predominate.

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