Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Proteolytic cleavage of Coronavirus spike proteins at the appropriate time and location results in efficient virus entry activation. Type II transmembrane serine proteases (TTSPs), specifically, transmembrane protease serine 2 (TMPRSS2) when expressed on target cells, enhance SARS coronavirus entry by activating spike cleavage. This study investigated the effect of TTSPs expressed in Coronavirus producer cells. Murine Hepatitis Virus strain A59 (MHV A59) viruses produced in the absence of TMPRSS2 required target cell protease activity - either cell surface serine proteases or endosomal acidophilic proteases - for entry. MHV A59 viruses produced in the presence of TMPRSS2 were less infectious overall, but a portion of the viruses contained "pre-primed" Spikes and were activated for entry in the absence of target cell protease activity. These findings indicate that coronaviruses can be proteolytically activated either in virus-producing cells or target cells and the timing of spike cleavage is crucial to virus infectivity.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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Virology Commons

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