Research Program Summary

Understanding how viruses evolve as they replicate and spread in the human population is fundamentally important for effective disease control. Viruses with segmented, RNA genomes can undergo reassortment during co-infection, resulting in progeny with segments derived from more than one parent. These exchanges allow viruses to acquire advantageous genes and rapidly adapt to selective pressures. Yet, segment exchange between divergent strains requires that critical protein-protein interactions be maintained during viral replication. As such, gene reassortment is a mixed blessing-the advantage of increasing diversity is balanced by the disadvantage of unlinking co-evolved proteins that operate best when kept together. My lab's research seeks to better understand the mechanism of gene reassortment for rotaviruses, which are segmented, double-stranded RNA viruses and important causes of severe gastroenteritis in young children. Specifically, we employ sequence-based and structure-function approaches to investigate the influence of viral protein-protein interactions on (i) the generation of rotavirus reassortants during co-infection and (ii) the fitness of reassortant strains in nature. These studies will enhance our ability to predict strain emergence and aid in rational vaccine design.

Education and Training

• Vanderbilt University: Ph.D.
• National Institute of Allergy and Infectious Disease: Postdoctoral fellowship

Previous Positions

• National Institutes of Allergy and Infectious Diseases, NIH
  Senior Research Fellow, Laboratory of Infectious Diseases

Selected Publications

• McDonald SM, Patton JT. (2011). Assortment and packaging of the segmented rotavirus genome. Trends in Microbiology, 19:136-44.
• McDonald SM, Patton JT. (2011). Rotavirus VP2 core shell regions critical for polymerase activation. J Virol, 85(7):3095-105.
• Rippinger CM, Patton JT, McDonald SM. (2010). Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E. Virology, 405:201-23.
• McDonald SM, Aguayo D, Gonzalez-Nilo FD, Patton JT. (2009). Shared and group-specific features of the rotavirus RNA polymerase reveal potential determinants of gene reassortment restriction. Journal of Virology, 83:6135-6148.
• McDonald SM, Tao XJ, Patton JT. (2009). The ins and outs of four-tunneled RNA-dependent RNA polymerases. Current Opinions in Structural Biology, 19:775-782.
• McDonald SM, Matthijnssens J, McAllen JK, Hine E, Overton L, Wang S, Lemey P, Zeller M, Van Ranst M, Spiro DJ, Patton JT. (2009). Evolutionary dynamics of human rotaviruses: balancing reassortment with preferred genome constellations. PLoS Pathogens, 5(10):e1000634.
• Heiman EM*, McDonald SM*, Barro M, Taraporewala ZF, Bar-Magen, Patton JT *co-first authors. (2008). Group A human rotavirus genomics: evidence that gene constellations are influenced by viral protein interactions. Journal of Virology, 82:11106-11116.