Medical Microbiology and Immunology : Isabel Novella, Ph.D.

Isabel Novella studies the evolution of viruses and how this knowledge can help fight viral infections. Vesicular stomatitis virus (VSV) is used as a model to study specific aspects of virus evolution and general issues of population genetics. VSV is grouped together with important pathogens (measles, influenza, poliovirus, HIV, hepatitis A, B and C viruses, etc.) among viruses whose genomic information is stored in RNA instead of DNA. This is important because RNA replication is error-prone, and therefore many mutations are constantly produced that allow extremely rapid evolution. We carry out experiments in which we allow virus replication under different conditions and analyze how these different conditions affect changes in fitness (replicative ability) and in genome sequences. The tools of molecular biology can now be used to test how different mutations may or may not cause specific phenotypes.

Isabel Novella received her Masters and Ph.D. degrees at the University of Oviedo, Spain, working on the physiology and genetics of Streptomyces and other actinomycetes. She did postdoctoral work in Foot-and-Mouth Disease virus evolution with Dr. David Andreu (University of Barcelona, Spain) and Dr. Esteban Domingo (Center for Molecular Biology, Madrid, Spain). Later she joined the group of Dr. John J. Holland at UCSD and focused on evolution of RNA virus populations. Isabel joined the Department of Microbiology and Immunology in September 1998.

Current grant funding:
NIH (NIAID) - Determinants of RNA Virus Evolution

Representative publications:

Kuzmin, I.V., Novella, I.S., Dietzgen, R., Padhi, A. and Rupprecht, C.E..  The Rhabdoviruses: Biodiversity, phylogenetics and evolution.  Infection, Genetics and Evolution (in press).

Domingo, E., Escarmis, C., Menendez-Arias, L., Perales, C.,  Herrera, M., Novella, I.S. and Holland, J.J.  Viral quasispecies dynamics: interactions and pathogenesis.  In Origin and Evolution of Viruses. Second Edition.  E. Domingo, C. Parrish and J.J. Holland (eds.) (2008).

Novella, IS, Dutta, RN, Wilke, CO.  (2008) A linear relationship between fitness and the logarithm of the critical bottleneck size in vesicular stomatitis virus populations.  J. Virol. Oct 1; 82:12589-12590. 

Presloid, J.B., Ebendick-Corpus, E.C., Zarate, S. and Novella, I.S.  (2008) Antagonistic pleiotropy involving promoter sequences in a virus.  J Mol Biol. 
Oct; 382(2):342-352. 

Dutta, R.N., Rouzine, I.M., Smith, S.D., Wilke, C.O. and Novella, I.S. (2008) Rapid adaptive amplification of preexisting variation in an RNA virus.
J. Virol. May; 82(9):4354-4352.   

Novella, I.S., Ebendick-Corpus, B.E., Zarate, S. and Miller, E.L. (2007)  Emergence of mammalian-adapted vesicular stomatitis virus from persistent infections of insect-vector cells.  J. Virol.  Jun; 81(12):6664-6668. 
 
Wilke, C.O., Forster, R. and Novella, I.S. (2006) Quasispecies in time-dependent environments. In Curr. Top. Microbiol. Immunol., E. Domingo (ed.), 299, pgs 33-50.

Novella, I.S., Gilbertson, D.L., Borrego, B., Domingo E., and Holland, J.J. (2005) Adaptability costs in immune escape variants of vesicular stomatitis virus. Virus Research, 107:27-34.

Novella, I.S., Ball, L.A., and Wertz, G.W. (2004) Fitness analyses of vesicular stomatitis virus strains with rearranged genomes reveal replicative disadvantages. J. Virol., 78:9837-9841.

Zárate, S. and Novella, I.S (2004) Vesicular stomatitis virus evolution during alternation between persistent infection in insect cells and acute infection in mammalian cells is dominated by the persistence phase. J. Virol., 78:12236-12242.

Novella, I.S., and Ebendick-Corpus, B.E. (2004) Molecular basis of fitness loss and fitness recovery in vesicular stomatitis virus. J. Mol. Biol., 342:1423-1430.

Novella, I.S., Zárate, S., Ebendick-Corpus, B.E., Metzger, D. (2004) Positive selection of synonymous mutations in an RNA virus. J. Mol. Biol., 342:1415-1421.

Novella, I.S., Reissig, D.D. and Wilke, C.O. (2004) Density-dependent selection in vesicular stomatitis virus. J. Virol., 78:5799-5804.

Wilke, C.O., Reissig, D.D. and Novella, I.S. (2004) Replication at periodically changing multiplicity of infection promotes stable coexistence of competing viral populations. Evolution, 58:900-905.

Novella, I.S. (2004) Negative effect of genetic bottlenecks on the adaptability of vesicular stomatitis virus. J. Mol. Biol., 336:61-67.

Novella, I.S. (2003) Contributions of vesicular stomatitis virus to the understanding of RNA virus evolution. Current Opinion in Microbiology, 6:1-7.

Wilke C.O., Novella, I.S. (2003) Phenotypic mixing and hiding may contribute to memory in viral quasispecies. BMC Microbiol., 3:11.

Quer, J., Hershey, C.L., Domingo, E., Holland, J.J. and Novella, I.S. (2001) Contingent neutrality in competing viral populations. J. Virol., 75:7315-7320.

Novella, I.S., Quer, J., Domingo, E. and Holland, J.J. (1999) Exponential fitness gains are limited by bottleneck effects. J. Virol., 73:1668-1671.

Novella, I.S., Hershey, C.L., Escarmis, C., Domingo, E. and Holland, J.J. (1999) Lack of evolutionary stasis of an arbovirus during alternating replication in mammalian and insect cells. J. Mol. Biol., 287:459-465.