PhD Projects » ESR 2: Mechanism of coordinated incorporation of segmented virus genomes into viral particles

Rithu Paul Stansilaus

I’m Rithu Paul Stansilaus, from India. I was introduced to viruses during my Bachelors in General Microbiology and instantly became fascinated by the complexities of a viral infection and its impact on global health. Determined to pursue a career in virology, I did a Masters in Clinical Virology from India where I studied antiviral properties of phytoconstituents against HSV and Adenoviruses. This was an exciting opportunity because I realised the endless applications of translational virology. However, following my Masters, after three years of working in diagnostic virology, I wanted to switch to translational research, which then prompted me to study Infection Biology, at the University of Glasgow, Scotland. My research project on chromosomal inheritance of Herpesvirus-7 helped me understand the significance of computational tools in biology which eventually paved my way to this PhD ooportunity.

During my PhD, I will study the packaging mechanism of Influenza A viruses at the University of Strasbourg and collaborate with ESR-2 by using viruses with computationally predicted pandemic potential to help develop therapeutic agents.

Outside of work, I love being a wayfarer honing my amateur photography skills, watching Disney movies and pencil sketching.

Field:
Virology
Host institution:
National Center for Scientific Research (CNRS), France
Local supervisor:
Dr. Roland Marquet (CNRS)
Local co-supervisor:
Prof. Laurence Despons (CNRS)
Project partners:
Gabriel Lovate (ESR 1)
Liuwei Wang (ESR 8)
Work packages:
WP 1.4 Virus regulation
WP 2.1 Microevolution: Virus quasispecies

Project description

Genetic reassortment between divergent IAVs in the host is a highly biased process in which only a small fraction of all possible genotypes are efficiently produced. This restriction is due to the limited compatibility between packaging signals of divergent IAVs and the limited conservation of RNA-RNA interactions required for genome packaging, but might also be influenced by the host as environment. Thus, analyses of genetic reassortment not only shed light on how viruses with pandemic potential are produced, but also provides crucial information about the coordinated incorporation of the segmented IAV genome.

Therefore, we will:

• Systematically generate reassortants between two human IAVs that will contain seven segments from a parental H1N1 virus and one segment from a parental H3N2 virus.
• Compare the secondary structure of the genomic RNA segments in the two parental and up to eight selected reassortant viruses grown in human cells using chemical probing (SHAPE-MAP). This analysis will be performed with ESR 4 and highlights differences in RNA-RNA interactions between parental and reassortant viruses. These experimental data will be used by ESR 1 to predict packaging signals.
• We will next experimentally verify ESR 1 packaging predictions.
• Finally, we will generate antivirally active biochemical substances that specifically interfere with RNA-RNA interactions between genomes, such as locked nucleic acids (LNA).

Doctorate will be awarded at University of Strasbourg.

@article{nokey,

title = {The influenza A virus genome packaging network - complex, flexible and yet unsolved},

author = {Celia Jakob and Rithu Paul-Stansilaus and Martin Schwemmle and Roland Marquet and Hardin Bolte},

doi = {10.1093/nar/gkac688},

year  = {2022},

date = {2022-08-22},

journal = {Nucleic Acids Res.},

abstract = {The genome of influenza A virus (IAV) consists of eight unique viral RNA segments. This genome organization allows genetic reassortment between co-infecting IAV strains, whereby new IAVs with altered genome segment compositions emerge. While it is known that reassortment events can create pandemic IAVs, it remains impossible to anticipate reassortment outcomes with pandemic prospects. Recent research indicates that reassortment is promoted by a viral genome packaging mechanism that delivers the eight genome segments as a supramolecular complex into the virus particle. This finding holds promise of predicting pandemic IAVs by understanding the intermolecular interactions governing this genome packaging mechanism. Here, we critically review the prevailing mechanistic model postulating that IAV genome packaging is orchestrated by a network of intersegmental RNA-RNA interactions. Although we find supporting evidence, including segment-specific packaging signals and experimentally proposed RNA-RNA interaction networks, this mechanistic model remains debatable due to a current shortage of functionally validated intersegmental RNA-RNA interactions. We speculate that identifying such functional intersegmental RNA-RNA contacts might be hampered by limitations of the utilized probing techniques and the inherent complexity of the genome packaging mechanism. Nevertheless, we anticipate that improved probing strategies combined with a mutagenesis-based validation could facilitate their discovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@misc{nokey,

title = {Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses},

author = {Rithu Paul-Stansilaus},

year  = {2022},

date = {2022-04-13},

howpublished = {Oral presentation at 3rd ResaFlu meeting 2022},

keywords = {},

pubstate = {published},

tppubtype = {presentation}

}

@misc{nokey,

title = {Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses},

author = {Rithu Paul-Stansilaus},

year  = {2022},

date = {2022-04-11},

howpublished = {Poster at XXIVemes Journées Francophones de Virologie 2022},

keywords = {},

pubstate = {published},

tppubtype = {presentation}

}