Work

RNA Polymerase Mutations Selected during Experimental Evolution Enhance Replication of a Hybrid Vaccinia Virus with an Intermediate Transcription Factor Subunit Replaced by the Myxoma Virus Ortholog

Year: 2018

Type: article

Abstract: Previous studies demonstrated the experimental evolution of vaccinia virus (VACV) following deletion of a host range gene important for evasion of host immune defenses. We have extended experimental evolution to essential genes that cannot be deleted but could be replaced by a divergent orthologous gene from another poxvirus. Replacement of a VACV transcription factor gene with one from a distantly related poxvirus led to decreased fitness as evidenced by diminished replication. Serially passaging the hybrid virus at a low multiplicity of infection provided conditions for selection of adaptive mutations that improved replication. Notably, these included five independent mutations of the largest and second largest RNA polymerase subunits. This approach should be generally applicable for investigating adaptation to swapping of orthologous genes encoding additional essential proteins of poxviruses as well as other viruses.

Source: Journal of Virology

DOI: 10.1128/jvi.01089-18

Authors: Carey A. Stuart, Erik K. Zhivkoplias, Tatiana G. Senkevich, Linda S. Wyatt, Bernard Moss

Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases

Language: English

Topic: Evolution and Genetic Dynamics

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Awards: G713713313, G9000229020