We study the replication and innate immune responses to Paramyxoviruses – a remarkably diverse family of negative-strand RNA viruses, some of which are the most ubiquitous disease-causing viruses of humans and animals. This work includes the development of vectors for therapy or vaccination that are based on novel properties of the viral genomes and proteins. In addition, we have expanded our focus to include viral immunology projects (interferon and complement) with the bioterrorism agent Nipah virus and the pathogenic bunyaviruses.

Our lab projects can be divided into three general areas:

1)    Interactions of negative strand RNA viruses with interferon and complement immune pathways. We address the questions of how these viruses first activate and then suppress important innate immune pathways in order to successfully replicate. This involves studies to understand the viral factors that induce interferon and complement responses, as well as the cellular sensors and pathways that respond, suppress replication, and neutralize virus.

2)    Developing of novel viral vectors for tumor therapy. We are taking advantage of inherent properties of the viruses we study to design novel vectors for controlled killing of tumor cells. This includes modifying the viral glycoproteins to produce vectors with enhanced ability to spread through a population of tumor cells. In addition, viral mutants which are defective in suppression of innate immunity are being tested for their ability to spread in tumor cells while retaining restricted growth in normal cells.

3)    Development of vaccine vectors based on paramyxoviruses. Viral vectors can be potent inducers of innate and adaptive immunity, but also can cause disease in some cases. We are exploiting unique properties of some of these paramyxoviruses to develop new delivery vehicles that balance attenuated replication with induction of strong immunity to an engineered antigen.

Recent Publications

  1. Kim, J, Holbrook BC, Hayward SL, Blevins LK, Jorgensen M, Kock ND, De Paris K, D’ Agostino R, Aycock ST, Mizel SB, Parks GD, and Alexander-Miller MA. 2015. Inclusion of flagellin during vaccination against influenza enhances recall responses in nonhuman primate neonates. J Virol 89: 7291-7303.
  2. Holbrook BC, Kim JR, Blevins LK, Jorgensen MJ, Kock ND, D’Agostino R, Mizel SB, Aycock ST, King SB, Parks GD, and Alexander-Miller MA. 2016. A novel R848-conjugated inactivated influenza virus vaccine is efficacious and safe in a neonate nonhuman primate model. J. Immunol 197:555-564.
  3. Li, Y, Johnson, JB, and Parks GD. 2016. Parainfluenza virus upregulates CD55 expression to produce virions with enhanced resistance to complement neutralization. Virology 497:305-313.
  4. Holbrook BC, D’Agostino RB Jr, Parks GD, and Alexander-Miller MA. 2016. Adjuvanting an inactivated influenza vaccine with flagellin improves the function and quantity of the long-term antibody response in a nonhuman primate neonate model. Vaccine 34:4712-7
  5. Fox CR and Parks GD. 2018. Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA Damaging Agents: Implications for Oncolytic Virus Therapy J. Virol. 92: e01948-17.
  6. Li, Y, and Parks GD. 2018. Relative contribution of cellular complement inhibitors CD59, CD46 and CD55 to Parainfluenza virus 5 inhibition of complement-mediated neutralization. Viruses 10:219
  7. Mazar J, Li Y, Rosado A, Phelan P, Kedarinath K, Parks GD, Alexander KA, and Westmoreland, TJ. 2018. Zika virus kills human neuroblastoma cells and requires CD24. PlosOne, 13(7):e0200358
  8. Fox CR and Parks GD. 2019. Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Elicited by Infection with an Oncolytic Parainfluenza Virus” Viruses 11 (5) e431