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PMID: 1560524 Published · ppublish English Journal Article

Molecular characterization of a neuropathogenic and nonerythroleukemogenic variant of Friend murine leukemia virus PVC-211.

Journal of virology ·Vol. 66 ·No. 5 ·1992-05-00 ·Pages 2798-806

Masuda M, Remington MP, Hoffman PM, Ruscetti SK

Abstract

PVC-211 murine leukemia virus (MuLV) is a replication-competent, ecotropic type C retrovirus that was isolated after passage of the Friend virus complex through F344 rats. Unlike viruses in the Friend virus complex, it does not cause erythroleukemia but causes a rapidly progressive hind limb paralysis when injected into newborn rats and mice. We have isolated an infectious DNA clone (clone 3d) of this virus which causes neurological disease in animals as efficiently as parental PVC-211 MuLV. The restriction map of clone 3d is very similar to that of the nonneuropathogenic, erythroleukemogenic Friend murine leukemia virus (F-MuLV), suggesting that PVC-211 MuLV is a variant of F-MuLV and that no major structural alteration was involved in its derivation. Studies with chimeric viruses between PVC-211 MuLV clone 3d and wild-type F-MuLV clone 57 indicate that at least one determinant for neuropathogenicity resides in the 2.1-kb XbaI-ClaI fragment containing the gp70 coding region of PVC-211 MuLV. Compared with nonneuropathogenic ecotropic MuLVs, the env gene of PVC-211 MuLV encodes four unique amino acids in the gp70 protein. Nucleotide sequence analysis also revealed a deletion in the U3 region of the long terminal repeat (LTR) of PVC-211 MuLV clone 3d compared with F-MuLV clone 57. In contrast to the env gene of PVC-211 MuLV, particular sequences within the U3 region of the viral LTR do not appear to be required for neuropathogenicity. However, the changes in the LTR of PVC-211 MuLV may be responsible for the failure of this virus to cause erythroleukemia, because chimeric viruses containing the U3 region of F-MuLV clone 57 were erythroleukemogenic whereas those with the U3 of PVC-211 MuLV clone 3d were not.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Animals, Newborn Base Sequence Cloning, Molecular Friend murine leukemia virus/genetics,pathogenicity Genes, env/genetics Genetic Variation Genome, Viral Hindlimb/pathology Leukemia, Erythroblastic, Acute/genetics,pathology Leukemia, Experimental/genetics,pathology Mice Molecular Sequence Data Paralysis/etiology Protein Processing, Post-Translational Rats Repetitive Sequences, Nucleic Acid/genetics Restriction Mapping Sequence Homology, Nucleic Acid Tumor Cells, Cultured Viral Proteins/metabolism
Chemicals
Viral Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Masuda M
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201.
Remington M P
Hoffman P M
Ruscetti S K
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.5.2798-2806.1992
Published
1992-05-00
Pages
2798-806
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC241036
Subset
IM
Databases
GENBANK
M81185
External Links
PubMed source DOI: 10.1128/JVI.66.5.2798-2806.1992 PMC Full Text View journal details
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