Shape-shifting Ebola Virus Protein Relies on Human RNA for Changing Shape
Millions of proteins exist in our bodies, and they are all governed by the human genome. These proteins have as many different shapes and functions as they are in number. Scientists have found that the shape that proteins fold into also determines their function.
Cell Reports has published a new study regarding the Ebola virus and its unique protein mechanisms. The La Jolla Institute for Immunology scientists discovered that although the virus has genes that encode just 8 proteins, many more functions (dozens) take place during the course of its lifecycle. VP40 is one of the critical proteins present in the virus. In the human cell, it utilizes molecular triggers to transform into various tools for different functions.
Erica Ollman Saphire is LJI’s Ph.D.-qualified professor, the study’s co-leader, and one of the members of the LJI Center for Infectious Disease and Vaccine Research. She spoke about the altering structures of the VP40 protein in the Ebola virus, enabling it to perform different functions at different times.
The unique string-like appearance of Ebola is also due to the VP40 protein, which, as Saphire’s experiments show, can take different shapes – a wreath-like shape (octamer) or a butterfly-like appearance (dimer). Transformations between the 2 forms are caused by dramatic rearrangements within the Shape-shifting Ebola Virus protein structure. While the dimeric structure enables the construction, emergence, and release of new viruses, the octameric form controls the other steps of the life cycle in infected cells.
This research study has found the reason for such structural changes. It has been discovered that particular human mRNA is sensed by the VP40 protein, relying on that mRNA for dimer-octamer transformation.
Scripps Research Professor Kristian Andersen (Ph.D.) was approached by Saphire for the deep sequencing of mRNAs chosen and trapped by VP40 within the human cells. The most commonly chosen sequences by Shape-shifting Ebola Virus protein VP40 were in the mRNA’s untranslated region.
The study’s co-first authors Sara Landeras Bueno (Ph.D.) and Hal Wasserman (Ph.D.), who are postdoctoral fellows at the Saphire lab both got a peek at the dimer-octamer transforming action through the purified VP40 protein taken in test tubes. The same conformational alteration seen in high-resolution VP40 structures as adenine and guanine-rich human mRNA sequences triggered. This was found by examining different mRNA combinations.
Landers Bueno said that it was a pleasant surprise that host cell RNA and not viral RNA triggers the transformation. This is an example of a parasite-like action by the virus.
The basis of information-encoding in the genome was also revealed. The mechanism of VP40 deployment is also controlled by the Ebola virus apart from genetic code controls. Saphire confirmed the existence of an additional layer of programming.
VP40 as a Shape-shifting Ebola Virus protein satisfies a sophisticated system of demands for Ebola infection. Not much alteration is anticipated. A specific attack on VP40 would render the virus helpless. Wasserman further clarified that the octameric functioning had mysterious aspects with regards to the regulation mechanism. However, it is more important to understand further how viral replication in Ebola is regulated by the VP40 structure. Saphire is extremely curious about the existence of similar “structural plasticity”-containing proteins in other viruses and organisms in general. She also wonders if such a phenomenon is more common than presently thought.
