Dr. Johnson’s research seeks to understand how viral proteins manipulate the host cell to facilitate infection. Focusing on the nucleocapsid protein of coronaviruses (CoVs), Dr. Johnson’s work utilizes reverse genetic systems to generate recombinant coronaviruses harboring mutations of interest. Each mutant is then characterized using in vitro and in vivo models of infection. Dr. Johnson has three ongoing research projects.

• Define how variant mutations in nucleocapsid augment SARS-CoV-2 pathogenesis. Since its emergence, SARS-CoV-2 has continued to evolve, resulting in distinct variants of concern (VoC). The appearance of VoCs has proven a challenge for pandemic mitigation efforts, resulting in enhanced transmission and breakthrough cases in vaccinated individuals. Consequently, understanding the unique mutations of each VoC is a pressing concern for the global public health. The overall goal of this project is to determine the significance of mutations in SARS-CoV-2 nucleocapsid found in VoCs.
• Identify and characterize virion-associated post-translational modifications. SARS-CoV-2 structural proteins are known to harbor a numerous post-translational modifications (PTMs), including phosphorylation, glycosylation, and ubiquitination. However, to date all studies published within the literature have examined PTMs within the cell. The goal of this project is to identify PTMs on CoV structural proteins found within the extracellular virion. Virion-associated and intracellular modification patterns are then compared, and the importance of unique or enriched extracellular PTMs to CoV infection determined.
• Characterize SARS-CoV-2’s antagonism of stress granule formation. Stress granules are large cytoplasmic aggregates of stalled translation initiation complexes that form in response to cellular stresses, including viral infection. Because stress granules inhibit the translation of viral proteins, viruses have evolved a wide variety of mechanisms for subverting their function. SARS-CoV-2 nucleocapsid has been shown to bind to several stress granule proteins, though the precise consequences on SARS-CoV-2 infection are unclear. The goal of this project is to characterize nucleocapsids antagonism of stress granule formation during the infection of SARS-CoV-2 and other coronaviruses.

SARS-CoV-2 variants, zoonotic coronaviruses, reverse genetic systems, coronavirus nucleocapsid, posttranslational modifications, molecular mechanisms of infection.

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