The Evolutionary Pathway to Virulence of an RNA Virus.
Paralytic polio once afflicted almost half a million children each year. The attenuated oral polio vaccine (OPV) has enabled world-wide vaccination efforts, which resulted in nearly complete control of the disease. However, poliovirus eradication is hampered globally by epidemics of vaccine-derived polio. Here, we describe a combined theoretical and experimental strategy that describes the molecular events leading from OPV to virulent strains. We discover that similar evolutionary events occur in most epidemics. The mutations and the evolutionary trajectories driving these epidemics are replicated using a simple cell-based experimental setup where the rate of evolution is intentionally accelerated. Furthermore, mutations accumulating during epidemics increase the replication fitness of the virus in cell culture and increase virulence in an animal model. Our study uncovers the evolutionary strategies by which vaccine strains become pathogenic and provides a powerful framework for rational design of safer vaccine strains and for forecasting virulence of viruses. VIDEO ABSTRACT.
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel. Electronic address: sternadi@post.tau.ac.il.
Adi
A
Stern
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Ming Te
MT
Yeh
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel.
Tal
T
Zinger
Division of Virology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.
Matt
M
Smith
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Caroline
C
Wright
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv 6997801, Israel.
Guy
G
Ling
Department of Integrative Biology; Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
Rasmus
R
Nielsen
Division of Virology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.
Andrew
A
Macadam
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: raul.andino@ucsf.edu.
Raul
R
Andino
D000818:Animals; D005075:Biological Evolution; D051379:Mice; D010802:Phylogeny; D011051:Poliomyelitis / Q000517:prevention & control / Q000821:virology*; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity*; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects* / Q000145:classification / Q000235:genetics* / Q000276:immunology
D011055:Poliovirus Vaccine, Oral