NDLI: Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in transformation

Content Provider	Springer Nature Link
Author	Hull, Stacey Lim, Joohyun Hamil, Alexander Nitta, Takayuki Fan, Hung
Copyright Year	2012
Abstract	Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a transmissible lung cancer in sheep. A unique feature is that JSRV envelope protein is also the oncogene for this virus. Previous studies have identified the cytoplasmic tail (CT) of the envelope transmembrane (TM) protein as critical for transformation although other regions of Env have also been implicated. In this study, the roles of other Env regions in transformation were investigated. Chimeras between JSRV Env and the Env of a related non-oncogenic endogenous retrovirus (enJSRV, 5F16) were used. A chimera containing the membrane-spanning region (MSR) of enJSRV inserted into JSRV Env showed substantially reduced transformation, indicating that the MSR plays a role in transformation. Transformation by this chimera was highly dependent on both Ras/Raf/MEK/MAPK and PI3K/Akt/mTOR signaling. A chimera containing the two amino acids in the TM ectodomain that distinguish JSRV and enJSRV showed modestly reduced transformation. Chimeras in the SU protein indicated that the amino terminal region of SU contributes to transformation, while the C-terminal part is not important. To test if Env trimerization is important for transformation, we mutated a leucine-rich sequence in the putative trimerization domain in the ectodomain of TM (Tri-M). This mutant could not transform cells and it did not oligomerize. However, Tri-M could complement a non-transforming mutant CT mutant (Y590F) so oligomerization is not necessary for at least some aspects of transformation. These experiments provide new insight into the regions and residues of JSRV Env protein necessary for oncogenic transformation.
Starting Page	508
Ending Page	517
Page Count	10
File Format	PDF
ISSN	09208569
Journal	Virus Genes
Volume Number	45
Issue Number	3
e-ISSN	1572994X
Language	English
Publisher	Springer US
Publisher Date	2012-08-04
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Retrovirus Envelope Jaagsiekte sheep retrovirus Transformation Mutations Medical Microbiology Virology Plant Sciences
Content Type	Text
Resource Type	Article
Subject	Virology Genetics Medicine Molecular Biology

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ANALYSIS OF JAAGSIEKTE SHEEP RETROVIRUS (JSRV) ENVELOPE PROTEIN DOMAINS IN TRANSFORMATION

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ANALYSIS OF JAAGSIEKTE SHEEP RETROVIRUS (JSRV) ENVELOPE PROTEIN DOMAINS IN TRANSFORMATION

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