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Rev HIV Protein [Part 2]

Feature contributed by Leonid Gitlin (UCSF)
February 2015

Rev is an HIV protein which helps the virus export its unspliced messages and genomes to the cytoplasm.  Now, a pair of reports from the laboratories of Alan Frankel and Yifan Cheng (UCSF) illuminate new facets of Rev. 

[Report 2]
Booth et al. (http://elifesciences.org/content/3/e04121) address the other interaction of Rev - the one with the nuclear export receptor Crm1.  This first look at the assembled HIV nuclear export complex by single-particle electron microscopy indicates that human Crm1 binds to the Rev-RRE complex as a dimer. While unexpected, this finding explains a long-standing enigma of rodent Crm1, which, while very similar to the human ortholog, does not support HIV virion production at similar levels. Additionally, the binding site of Rev-RRE is quite distinct from the previously known Crm1 cargo site. While this may indicate that HIV found a new binding interface on Crm1, the authors suggest that there is more to the host biology of Crm1 than previously appreciated and that Crm1 dimers may have additional roles in the cell.

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Rev HIV Protein [Part 1]

Feature contributed by Leonid Gitlin (UCSF)
February 2015

Rev is an HIV protein which helps the virus export its unspliced messages and genomes to the cytoplasm.  Now, a pair of reports from the laboratories of Alan Frankel and Yifan Cheng (UCSF) illuminate new facets of Rev. 

[Report 1]
Bhargavi Jayaraman et al. (http://elifesciences.org/content/3/e04120) show that Rev-Rev dimer interaction is altered upon the dimer binding to RRE (HIV's RNA Response Element, which is the target of Rev).  Like a pair of scissors, the pair of Rev monomers can alter the angle at which they interact, as their "blades" bind target RNA. In this way, RRE RNA can guide and shape the conformation of the Rev dimer and the eventual architecture of the subsequent Rev multimer. The authors posit that this kind of interaction can be key to using an apparently simple protein (Rev) to build an extremely versatile RNP.

 

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Raccoon Polyomavirus

Feature contributed by Paul Luciw (UC Davis)
January 2015

Despite decades of illuminating studies on viral mechanisms of persistence, immune evasion, and the remarkable capacity for viruses to manipulate the cell cycle, there is still debate over the role of viruses in malignancy. The Polyomaviridae are one of the small number of DNA viruses that have been shown experimentally to produce malignant transformation.  Infections with this family of viruses are widespread in human and animal populations, and while generally associated with silent infections, they can cause severe disease in a small proportion of people or animals.  Dr. Patricia Pesavento and her laboratory studies a polyomavirus (RacPyV) isolated from neuroglial tumors in free-ranging raccoons.  RacPyV is present in 100% of the tumors, its DNA genome exists in high copy number, and the tumors are in an anatomically consistent site of individual animals, within or adjacent to the olfactory tract.  The viral oncogenic protein large T-antigen (LT) is heavily expressed in natural tumors, in cell lines derived from the tumors, and in raccoon tumors in a xenograft model in mice. proposes that RacPyV infects and transforms raccoon neural progenitor cells. The raccoon virus is phylogenetically conserved within the same clade as Merkel cell polyomavirus (MCPyV), the causative and integrated viral agent of Merkel cell carcinoma (MCC) in humans.  Dr. Kevin Woolard, a neuropathologist at UCD, has shown that like MCPyV induced MCC, the raccoon brain tumors highly express the oncogenes c-myc and survivin.  Unlike MCPyV, RacPyV is not integrated, but is nonetheless stably maintained as an episome in all tumors and in tumor cell lines.  Also novel for PyV studies so far, RacPyV virions, which are not found in naturally occurring tumors, are present in the stable cell lines that Dr. Woolard has derived from the tumors.  This is enigmatic in the face of the long accepted dogma that cells which are malignantly transformed by polyomavirus produce no infectious virus. The complex pathogenesis of oncogenesis of the polyomaviruses in their respective susceptible hosts provides diagnostic and clinical challenges in animals and people, requiring a “one health approach” to investigate the contribution that the virus makes to transformation or tumor maintenance and to test and develop intervention approaches.

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