RNA sequencing provides evidence for allelism of determinants of the N-, B- or NB-tropism of murine leukemia viruses

Rommelaere, Jean; Donis-Keller, Helen; Hopkins, Nancy

doi:10.1016/0092-8674(79)90186-7

Cited by 64 publications

(38 citation statements)

References 16 publications

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“…The N/D ratio was 0-67 to 0.87 for Ki-MSV rescued by N-tropic virus and 0.38 to 0.49 for Ki-MSV rescued by B-tropic virus (Table 1). This observation is consistent with previous results establishing the Fv-1 determinant as a viral structural protein (p30) (Failer & Hopkins, 1977;Hopkins et al, 1977;Gautsch et al, 1978;Rommelaere et al, 1979;Rassart et al, 1981;Ou et aL, 1983;DesGroseillers & Jolicoeur, 1983) and confirms the phenotypic mixing reported by Rein et al (1976).…”

supporting

confidence: 82%

Synthesis of Proviral DNA in Inbred Mouse-derived Clones of Cells Expressing Different Fv-1 Phenotypes

Iwamoto¹,

Masuda²,

Yasuda³

1985

Journal of General Virology

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SUMMARYFormation of proviral DNAs by B-tropic murine leukaemia viruses (MLVs) was examined in N-type and dually permissive mutant cells derived from two inbred mouse strains, DDD and G, both of which are N-type. In the N-type cells, formation of circular proviral DNA was strongly suppressed relative to that of linear DNA. Mutation resulting in loss of the N-type Fv-1 restriction resulted in efficient formation of circular DNA by the previously restricted B-tropic MLV. This showed that Fv-1 restriction and inhibition of closed circular DNA formation were controlled by the same gene. The efficiency of formation of circular proviral DNA by the defective Kirsten murine sarcoma virus was determined by the tropism of the helper virus.The RN A form of the retrovirus genome of murine leukaemia virus (MLV) is transcribed into linear and circular DNA duplexes after infection, and then integrated into the host chromosome. However, it is still unclear which of the free forms of viral DNA is the final precursor of the integrated form (Varmus, 1983). Study of the restriction exercised by the Fv-1 locus of mice has been found appropriate for studying this problem. The formation of circular but not linear DNA was suppressed in Fv

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supporting

confidence: 82%

Synthesis of Proviral DNA in Inbred Mouse-derived Clones of Cells Expressing Different Fv-1 Phenotypes

Iwamoto¹,

Masuda²,

Yasuda³

1985

Journal of General Virology

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“…However, a previous study showed that the introduction of the corresponding amino acid (Ala) from NB-tropic Mo-MLV did not give rise to an NBtropic virus (41). In contrast, genetic studies pointed to the involvement of a linked amino acid at position 105 (11,43). Similarly, the only NR-tropic virus investigated thus far showed a modification at position 114 (24).…”

Section: Resultsmentioning

confidence: 89%

“…Genetic studies initially suggested that the target for Fv1 restriction is the MLV capsid (CA) protein (20,43). Subsequent studies indicated that viral tropism is determined by a pair of adjacent amino acids, at positions 109 and 110, in CA (10,40).…”

mentioning

confidence: 99%

Retroviral Capsid Determinants of Fv1 NB and NR Tropism

Stevens¹,

Bock²,

Ellis³

et al. 2004

J Virol

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The specificity determinants for susceptibility to resistance by the Fv1 n and b alleles map to amino acid 110 of the murine leukemia virus CA protein. To study the interaction between Fv1 and CA, we examined changes in CA resulting in the loss of susceptibility to Fv1 resistance in naturally occurring NB-and NR-tropic viruses. A variety of amino acid changes affecting Fv1 tropism were identified, at CA positions 82, 92 to 95, 105, 114, and 117, and they all were mapped to the apparent exterior of virion-associated CA. These amino acids may form a binding surface for Fv1.The Fv1 gene is one of a series of mouse genes, originally described in the early 1970s, that control the susceptibility of mice to murine leukemia virus (MLV) infection (32,34 nr , found in a few inbred strains of mice and apparently also in some wild mice, restricts B-tropic MLV and some, but not all, N-tropic viruses (28,48). In this paper, we will refer to N-tropic viruses that are not restricted by Fv1 nr as being NR tropic.Fv1 acts in a cell-autonomous manner to restrict virus replication (44), but the precise mechanism for restriction is unclear. It has been shown that viral replication is blocked at a stage after virus entry into the cell and before the integration of newly synthesized viral DNA into the host genome (22, 41). The block to infection is not absolute in vitro, but the number of infected cells is reduced by a factor of 50 to 1,000 (17). When expressed at natural levels, e.g., in mouse fibroblast lines, neither Fv1 n nor Fv1 b shows significant in vitro restriction of NB-tropic MLV.Genetic studies initially suggested that the target for Fv1 restriction is the MLV capsid (CA) protein (20, 43). Subsequent studies indicated that viral tropism is determined by a pair of adjacent amino acids, at positions 109 and 110, in CA (10, 40). A more recent study has shown that position 110 is the most important residue for N and B tropism (29). N-tropic MLV has an Arg residue at this position, and B-tropic MLV has a Glu residue. The determinants for NB and NR tropism have not been fully characterized.The Fv1 gene was cloned a few years ago (3) and was found to have sequence similarity to a family of endogenous retroviruses called HERV-L (60% identity over 1.3 kb) or MuERV-L (1, 3). Based on its position within the element and the presence of a major homology region (3), Fv1 apparently encodes a Gag-related protein. Gag proteins bind tightly to each other via interaction domains during virus assembly (35), which suggests a possible mechanism for Fv1's action on MLV CA (16). To date, however, there is no direct evidence for the binding of Fv1 to CA. Biochemical analyses are greatly complicated by the extremely low natural expression levels of Fv1 in vivo. We have therefore taken a genetic approach to analyzing the viral determinants of NB and NR tropism, using a rapid fluorescence-activated cell sorting (FACS)-based approach for Fv1 testing (5), in an attempt to delineate the region(s) of CA that interacts with Fv1. MATERIALS AND METHODS Cel...

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“…This earlier shift in tropism pattern, (N-to B-tropic MuLV) might be related to the proposed models for generation of Btropic MuLV. and Rommelaere and co-workers (18) have shown that the difference between N-and NB-tropic MuLV might be due to subtle modifications of the p30 molecule (major core protein), and a single base change might be sufficient for this change. This change could be accomplished by mutation or recombination with other endogenous gag-like genes.…”

Section: Discussionmentioning

confidence: 99%

Genetic interactions in the spontaneous production of endogenous murine leukemia virus in low leukemic mouse strains.

McCubrey¹,

Risser²

1982

The Journal of Experimental Medicine

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The spontaneous expression of ecotropic murine leukemia virus (MuLV) in spleen cells of BALB/c, C57BL/6 (B6), and derivative mice was examined as a function of age. The patterns of spontaneous virus induction in vivo correlate with the patterns of virus induction in vitro, which result from the action of two loci, Inc-l and Inb-l (7). Whereas mice carrying Inc-l or Inb-l have similar phenotypes in vitro, they have significantly different phenotypes in vivo. Mice of the Inb-l+/+ genotype, e.g., B6, rarely expressed MuLV, and the titer of MuLV recovered from rare MuLV-positive mice of this genotype was usually low. Mice of the Inc-l+/+ genotype, e.g., BALB/c, expressed low amounts of MuLV early in life, however, from 6-12 mo of age approximately one-half of the Inc-l+/+ mice expressed virus, frequently of high titer. Equal numbers of N-tropic and B-tropic MuLV were recovered from Inb-l+ mice, but predominantly N-tropic MuLV was recovered from Inc-l+ mice. Strains that carry dominant (+) alleles at both Inc-l and Inb-l show higher titers of MuLV earlier in life than strains that carry only Inc-l or Inb-l. The presence of dominant alleles at both loci results in the appearance of predominantly N-tropic virus early in life. These results demonstrate that the principal determinants of spontaneous virus expression in these low leukemic strains of mice are the In loci or genes linked to them. A further inference that can be drawn from these studies is that the appearance of B-tropic virus is by no means a random process but rather results from predictable patterns of MuLV expression and alteration.

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RNA sequencing provides evidence for allelism of determinants of the N-, B- or NB-tropism of murine leukemia viruses

Cited by 64 publications

References 16 publications

Synthesis of Proviral DNA in Inbred Mouse-derived Clones of Cells Expressing Different Fv-1 Phenotypes

Synthesis of Proviral DNA in Inbred Mouse-derived Clones of Cells Expressing Different Fv-1 Phenotypes

Retroviral Capsid Determinants of Fv1 NB and NR Tropism

Genetic interactions in the spontaneous production of endogenous murine leukemia virus in low leukemic mouse strains.

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