publications

2023

1. J Virol

   Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production

   Sarah A. Clark, Angie Vazquez, Kelsey Furiya, and 11 more authors

   Journal of Virology, May 2023

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   Oncogenic virus infections are estimated to cause  15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors.

   @article{jvi.00506-23,
     title = {Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production},
     author = {Clark, Sarah A. and Vazquez, Angie and Furiya, Kelsey and Splattstoesser, Madeleine K. and Bashmail, Abdullah K. and Schwartz, Haleigh and Russell, Makaiya and Bhark, Shun-Je and Moreno, Osvaldo K. and McGovern, Morgan and Owsley, Eric R. and Nelson, Timothy A. and Sanchez, Erica L. and Delgado, Tracie},
     journal = {Journal of Virology},
     volume = {97},
     issue = {6},
     pages = {e00506-23},
     year = {2023},
     month = may,
     publisher = {American Society for Microbiology},
     doi = {10.1128/jvi.00506-23},
     url = {https://journals.asm.org/doi/abs/10.1128/jvi.00506-23},
     dimensions = {true},
   }