Institute for Integrative Systems Biology (I2SysBio)


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Viral mutation rates

(VirMut)


University of Valencia

Genetics Department

I2SysBio

FISABIO-CSISP

 

    VSV aggregate by TEM              
                        


Virus experimental evolution (Sanjuán lab)

Viruses

Viruses are excellent model systems for addressing basic evolutionary questions because they evolve fast in the lab, allowing us to do 'real time' evolutionary analyses. Viral evolution is also interesting per se, since it helps explaining disease emergence, drug resistance, immune escape, and other biomedically relevant processes. Moreover, viral evolution can be harnessed for applied research goals, such as improving the efficacy of therapeutic viruses used in cancer and for combating drug-resistant bacteria. We have recently worked with several viruses:



Vesicular stomatitis virus (VSV), a negative-stranded RNA virus belonging to the family Rhabdoviridae. As most RNA viruses, it has a small genome, a high per-base mutation rate, and low tolerance to mutations. In the wild, VSV is a concern for farmers in regions where it can infect livestock. In the lab, it has been extensively used as a tool for experimental evolution and for pseudotyping and vaccine production, among other applications. VSV also exhibits a natural tropism towards cancer cells, which has motivated research into its use as an oncolytic agent. We have shown that VSV virions can aggregate and be co-transmitted to the same cells, forming "collective infectious units".

Enteroviruses, a large genus of plus-strand RNA viruses, including poliovirus, coxsackieviruses, and rhinovirurses. Enteroviruses can use lipid vesicles for cell-to-cell transmission. This increases levels of coinfection and promotes virus-virus interactions.

Baculoviruses are large double-stranded DNA viruses infecting insects. They are transmitted among larva inside matrix proteins called occlusion bodies which, in many cases, contain multiple virions. This type of collective transmission may foster the establishment of interactions between different genetic variants of the virus. 

SARS-CoV-2. We are involved in several projects related to this emerging pathogen. First, we are analyzing wastewaters by RT-qPCR as a method for early and cost-effective epidemiological surveillance. Second, we are testing different compounds for their potential anti-viral activity. Third, we are collaborating with companies for testing virucidals. Fourth, we are investigating possible applications of antagonistic virus-virus interactions for combating the virus.

Bacteriophages
. We have recently embarked into a phage discovery project, specially for Klebsiella phages. We are also investigating phage-phage social-like interactions and how these interactions could help us design better phage cocktails for combating multi-drug-resistant bacteria.


HIV-1. We have conducted studies using sequence, immunologic, and structural data available from public repositories. We have also used  samples from patients to perform sequence analyses and we have complemented this approach with virus culturing systems to study the production of viral spontaneous mutations.


Hepatitis C virus. We have analyzed sequence datasets to investigate the effect of the interferon-ribavirin therapy on the viral mutation rate. We have also conducted in vitro replication experiments to learn more about the replication fidelity of this virus.

Human adenovirus 5, a double-stranded DNA virus, was the first virus to be licensed for oncolytic virotherapy. DNA viruses were long believed to exhibit high genetic stability, but recent findings contradict this view. We have investigated the molecular mechanisms at the origin of adenovirus genetic diversity.









Universitat de València, 2020