Details

Autor(en) / Beteiligte

• YUEN, P. H
• RYAN, E. A
• DEVROE, E
• WONG, P. K. Y

Titel

A single Glu62-to-Lys62 mutation in the Mos residues of the R7Δ447Gag-tMos protein causes the mutant virus to induce brain lesions

Ist Teil von

• Oncogene, 2001-02, Vol.20 (6), p.692-703

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

2001

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• We previously reported that R7Δ447, a 2954-base-pair (bp) laboratory-generated Moloney murine sarcoma virus, induced subcutaneous tumors in about 14% of infected mice but did not induce brain lesions. We now report that R7Δ447K, a spontaneous mutant of R7Δ447, induced brain lesions as well as subcutaneous tumors in all injected mice. The genomes of the two viruses differ in a single base pair: the deduced Glu62 of the Mos residue of the R7Δ447 Gag-tMos protein is changed to Lys62. More R7Δ447 than R7Δ447K focus-forming units were detected in both NIH3T3 and mouse cerebral vascular endothelial (MCVE) cells. However, R7Δ447K transformed NIH3T3 and MCVE cells more acutely than did R7Δ447. A distinctive feature that distinguished the morphologic transformation of R7Δ447- and R7Δ447K-infected MCVE cells is the markedly prolonged spindle-shaped phase exhibited by R7Δ447-infected MCVE cells. In addition, R7Δ447K was more efficient in inducing the phosphorylation of ERK1/2 than R7Δ447 in both MCVE and NIH3T3 cells. Moreover morphologic transformation was inhibited, and levels of phosphorylated ERK1/2 were reduced when R7Δ447- or R7Δ447K-infected NIH3T3 or MCVE cells were grown in the presence of the MEK1/2-specific inhibitor PD98095. Thus, we have identified a key residue in the Gag-tMos protein that profoundly affects activation of the Mos/MEK/ERK pathway, virus and cell replication, morphologic transformation in vitro and pathogenicity in vivo.