scholarly journals Substitution of Feline Leukemia Virus Long Terminal Repeat Sequences into Murine Leukemia Virus Alters the Pattern of Insertional Activation and Identifies New Common Insertion Sites

2005 ◽  
Vol 79 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Chassidy Johnson ◽  
Patricia A. Lobelle-Rich ◽  
Adriane Puetter ◽  
Laura S. Levy
Keyword(s):  
T Cell ◽  
Long Terminal Repeat ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Target Tissue ◽  
Parent Virus ◽  
New Genes ◽  
Insertion Sites ◽  
Murine Leukemia

ABSTRACT The recombinant retrovirus, MoFe2-MuLV (MoFe2), was constructed by replacing the U3 region of Moloney murine leukemia virus (M-MuLV) with homologous sequences from the FeLV-945 LTR. NIH/Swiss mice neonatally inoculated with MoFe2 developed T-cell lymphomas of immature thymocyte surface phenotype. MoFe2 integrated infrequently (0 to 9%) near common insertion sites (CISs) previously identified for either parent virus. Using three different strategies, CISs in MoFe2-induced tumors were identified at six loci, none of which had been previously reported as CISs in tumors induced by either parent virus in wild-type animals. Two of the newly identified CISs had not previously been implicated in lymphoma in any retrovirus model. One of these, designated 3-19, encodes the p101 regulatory subunit of phosphoinositide-3-kinase-gamma. The other, designated Rw1, is predicted to encode a protein that functions in the immune response to virus infection. Thus, substitution of FeLV-945 U3 sequences into the M-MuLV long terminal repeat (LTR) did not alter the target tissue for M-MuLV transformation but significantly altered the pattern of CIS utilization in the induction of T-cell lymphoma. These observations support a growing body of evidence that the distinctive sequence and/or structure of the retroviral LTR determines its pattern of insertional activation. The findings also demonstrate the oligoclonal nature of retrovirus-induced lymphomas by demonstrating proviral insertions at CISs in subdominant populations in the tumor mass. Finally, the findings demonstrate the utility of novel recombinant retroviruses such as MoFe2 to contribute new genes potentially relevant to the induction of lymphoid malignancy.

scholarly journals Differential disease restriction of Moloney and Friend murine leukemia viruses by the mouse Rmcf gene is governed by the viral long terminal repeat.

1991 ◽  
Vol 174 (2) ◽  
pp. 389-396 ◽  
Author(s):  
B K Brightman ◽  
Q X Li ◽  
D J Trepp ◽  
H Fan
Keyword(s):  
Long Terminal Repeat ◽  
Murine Leukemia Virus ◽  
Time Course ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Moloney Murine Leukemia Virus ◽  
Erythroid Progenitors ◽  
Equivalent Time ◽  
Induced Tumors ◽  
Murine Leukemia

Neonatal CxD2 (Rmcfr) and Balb/c (Rmcfs) mice inoculated with Moloney murine leukemia virus (M-MuLV) exhibited approximately equivalent time course and pathology for disease. CxD2 mice showed only slightly reduced presence of Moloney mink cell focus-forming virus (M-MCF) provirus as seen by Southern blot analysis compared to Balb/c mice. This lack of restriction for disease and spread of MCF was in sharp contrast to that seen for CxD2 mice inoculated with Friend murine leukemia virus (F-MuLV), where incidence of disease and propagation of MCFs were severely restricted, as previously reported. Inoculation of CxD2 mice with FM-MuLV, a recombinant F-MuLV virus containing M-MuLV LTR sequences (U3 and R), resulted in T cell disease of time course equal to that seen in Balb/c mice; there also was little restriction for propagation of MCFs. This indicated that presence of the M-MuLV long terminal repeat (LTR) was sufficient for propagation of MCFs in CxD2 mice. Differing restriction for F-MuLV vs. M-MuLV in CxD2 mice was explained on the basis of different "MCF propagator cells" for the two viruses. It was suggested that cells propagating F-MCF (e.g., erythroid progenitors) are blocked by endogenous MCF-like gp70env protein, whereas cells propagating M-MCF (e.g., lymphoid) do not express this protein on their surface. F-MuLV disease in CxD2 mice was greatly accelerated when neonates were inoculated with a F-MuLV/F-MCF pseudotypic mixture. However, F-MCF provirus was not detectable or only barely detectable in F-MuLV/F-MCF-induced tumors, suggesting that F-MCF acted indirectly in induction of these tumors.

scholarly journals A Moloney Murine Leukemia Virus-Based Retrovirus with 4070A Long Terminal Repeat Sequences Induces a High Incidence of Myeloid as Well as Lymphoid Neoplasms

2003 ◽  
Vol 77 (8) ◽  
pp. 4965-4971 ◽  
Author(s):  
Linda Wolff ◽  
Richard Koller ◽  
Xinrong Hu ◽  
Miriam R. Anver
Keyword(s):  
Long Terminal Repeat ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Moloney Murine Leukemia Virus ◽  
Neoplastic Disease ◽  
Broad Host Range ◽  
Genetically Engineered Mice ◽  
High Incidence ◽  
Murine Leukemia

ABSTRACT Retroviruses can be used to accelerate hematopoietic cancers predisposed to neoplastic disease by prior genetic manipulations such as in transgenic or knockout mice. The virus imparts a second neoplastic “hit,” providing evidence that the initial hit is transforming. In the present study, a unique retrovirus was developed that can induce a high incidence of myeloid disease and has a broad host range. This agent is a Moloney murine leukemia virus (Mo-MuLV)-based virus that has most of the U3 region of the long terminal repeat (LTR) replaced with that of retrovirus 4070A. Like Mo-MuLV, this virus, called MOL4070LTR, is NB-tropic and not restricted by Fv1 allelles. MOL4070LTR causes myeloid leukemias in ca. 50% of mice, a finding in contrast to Mo-MuLV, which induces almost exclusively lymphoid disease. The data suggest that the LTR of the 4070A virus expands the tissue tropism of the disease to the myeloid lineage. Interesting, MCF recombinant envelope was expressed in the lymphoid but not the myeloid neoplasms of BALB/c mice. This retrovirus has the potential for accelerating myeloid disease in genetically engineered mice.

scholarly journals Retrovirus transduction: generation of infectious retroviruses expressing dominant and selectable genes is associated with in vivo recombination and deletion events.

1983 ◽  
Vol 3 (12) ◽  
pp. 2180-2190 ◽  
Author(s):  
A L Joyner ◽  
A Bernstein
Keyword(s):  
Long Terminal Repeat ◽  
Thymidine Kinase ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Terminal Repeat ◽  
Moloney Murine Leukemia Virus ◽  
Murine Leukemia

We describe the generation of infectious retroviruses containing foreign genes by an in vivo recombination-deletion mechanism. Cotransfection into mouse cells of chimeric plasmids carrying a murine retrovirus 5' long terminal repeat and either the thymidine kinase (tk) gene of herpesvirus or the dominant selectable bacterial gene for neomycin resistance (neo), along with a clone of Moloney murine leukemia virus, results in the generation of infectious thymidine kinase or neomycin-resistant viruses. Expression of the selectable marker in these viruses can be regulated by the homologous transcriptional promoter of the gene, by the promoter contained within the Friend spleen focus-forming virus long terminal repeat, or by the simian virus 40 early region promoter. In all cases, the rescued viruses appeared to arise by recombination in vivo with Moloney murine leukemia virus sequences, resulting in the acquisition of the Moloney 3' long terminal repeat and variable amounts of the 3' adjacent Moloney genome. In two of the thymidine kinase constructs where tk was inserted 200 base pairs downstream from the long terminal repeat, the rescued viruses acquired a large part of the murine leukemia virus genome, including the region involved in packaging genomic RNA into virions. The generation of infectious neomycin-resistant virus is associated with deletions of simian virus 40 splicing and polyadenylation sequences. These results demonstrate that nonhomologous recombination and deletion events can take place in animal cells, resulting in the acquisition or removal of cis-acting sequences required for, or inhibitory to, retrovirus infectivity.

Mapping of a major osteomagenic determinant of murine leukemia virus RFB-14 to non-long terminal repeat sequences.

1997 ◽  
Vol 71 (1) ◽  
pp. 645-649 ◽  
Author(s):  
M Ostergaard ◽  
L Pedersen ◽  
J Schmidt ◽  
A Luz ◽  
J Lovmand ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Terminal Repeat ◽  
Repeat Sequences ◽  
Murine Leukemia

Retrovirus transduction: generation of infectious retroviruses expressing dominant and selectable genes is associated with in vivo recombination and deletion events

1983 ◽  
Vol 3 (12) ◽  
pp. 2180-2190
Author(s):  
A L Joyner ◽  
A Bernstein
Keyword(s):  
Long Terminal Repeat ◽  
Thymidine Kinase ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Terminal Repeat ◽  
Moloney Murine Leukemia Virus ◽  
Murine Leukemia

We describe the generation of infectious retroviruses containing foreign genes by an in vivo recombination-deletion mechanism. Cotransfection into mouse cells of chimeric plasmids carrying a murine retrovirus 5' long terminal repeat and either the thymidine kinase (tk) gene of herpesvirus or the dominant selectable bacterial gene for neomycin resistance (neo), along with a clone of Moloney murine leukemia virus, results in the generation of infectious thymidine kinase or neomycin-resistant viruses. Expression of the selectable marker in these viruses can be regulated by the homologous transcriptional promoter of the gene, by the promoter contained within the Friend spleen focus-forming virus long terminal repeat, or by the simian virus 40 early region promoter. In all cases, the rescued viruses appeared to arise by recombination in vivo with Moloney murine leukemia virus sequences, resulting in the acquisition of the Moloney 3' long terminal repeat and variable amounts of the 3' adjacent Moloney genome. In two of the thymidine kinase constructs where tk was inserted 200 base pairs downstream from the long terminal repeat, the rescued viruses acquired a large part of the murine leukemia virus genome, including the region involved in packaging genomic RNA into virions. The generation of infectious neomycin-resistant virus is associated with deletions of simian virus 40 splicing and polyadenylation sequences. These results demonstrate that nonhomologous recombination and deletion events can take place in animal cells, resulting in the acquisition or removal of cis-acting sequences required for, or inhibitory to, retrovirus infectivity.

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