Institute for Integrative Systems Biology (I2SysBio)

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Model viruses

Research tools

Publications

 

Viral mutation rates

(VirMut)


University of Valencia

Genetics Department

I2SysBio

FISABIO-CSISP

 

    VSV aggregate by TEM              
                        

Evolution and Health Research Unit

Sanjuán lab

Model viruses

Viruses are excellent model systems for studying evolution because they evolve fast under lab conditions, which allows us to do 'real time' analyses. Moreover, their relatively small genomes facilitate genetic manipulation and the study of the genetic basis of adaptation. We are now working both at the computational and experimental level 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 size, a high per-base mutation rate, and low tolerance to mutations. In the wild, VSV is of particular importance to farmers in regions where it can infect livestock. In the lab, it has been extensively used for experimental evolution. In the field of biomedical research, it has been shown that VSV possess a natural tropism for cancer cells, which has motivated research into its use as an oncolytic agent. We have recently shown that VSV virions can aggreagte and be co-transmitted to the same target cells, forming "collective infectious units".

Enteroviruses, a large genus of plus-strand RNA viruses, including poliovirus, coxsackieviruses, and rhinovirurses. It has been recently shown that enteroviruses can use large lipid vesicles for cell-to-cell transmission. This could increase levels of coinfection and promote 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 long-term interactions between different genetic variants of the 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 show high genetic stability, but recent findings contradict this view. We are investigating the molecular mechanisms at the origin of adenovirus genetic diversity.


HIV-1.  Given the huge amount of  information available for this virus, it constitutes an excellent model for studying  evolution at the molecular level. 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 laboratory culturing systems to study the process of viral spontaneous mutation.


Hepatitis C virus (HCV) constitutes a major global health issue. 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.

Bacteriophages. RNA (Qbeta, MS2, SP) and single-stranded DNA (phiX174, G4, f1/m13) coliphages, all of which infect the same host strain, thus allowing us to perform direct comparisons between viral species.







Universitat de València, 2018