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. Ganguli T, Johnson JB, Parks GD and Deora R. 2014. Bordetella BPS interactions with human complement pathways. Cellular Microbiol 16:1105-1118.
  2. Mayer AE, Johnson JB, and Parks GD. 2014. The neutralizing capacity of antibodies elicited by parainfluenza virus infection of African Green monkeys is dependent on complement. Virology 460:23-33.
  3. Khalil SM, Tonkin DR, Snead AT, Parks GD, Johnston RE, and White LJ. 2014. An alphavirus-based adjuvant enhances serum and mucosal antibodies, T cells and protective immunity to influenza virus in neonatal mice. J. Virol. 88:9182-9196.
  4. Johnson JB, Schmitt AP, and Parks GD. 2013. Point mutations in the paramyxovirus F protein that enhance fusion activity shift the mechanism of complement-mediated virus neutralization. J. Virol 87:9250-9259
  5. Parks GD and Alexander-Miller MA. 2013. Invited Review: Paramyxovirus activation and inhibition of innate immune pathways. J. Molec. Biol. 425:4872-4892.
  6. Johnson JB, Lyles DS, Alexander-Miller MA and Parks GD. 2012. Virion-associated CD55 is more potent than CD46 in mediating resistance of mumps virus and VSV to neutralization. J. Virol. 86:9929-9940.
  7. Biswas, M, Kumar S, Johnson J, Parks GD and Subbiah E. 2012. Incorporation of host complement regulatory proteins into Newcastle Disease virus enhances complement evasion. J. Virol. 86:12708-12716.
  8. Briggs CM and Parks GD. 2012. Mumps virus inhibits migration of primary human macrophages toward a chemokine gradient through a TNF-alpha dependent mechanism. Virology 433:245-252.
  9. Johnson JB, Aguilar H, Lee B, and Parks GD. 2011. Interactions of human complement with virus particles containing the Nipah virus glycoproteins. J. Virol. 85:5940-5948.
  10. Clark KM, Johnson JB, Kock ND, Mizel SB and Parks GD. 2011. Parainfluenza virus 5-based vaccine vectors expressing vaccinia virus VACV antigens provide long-term protection in mice from lethal intranasal VACV challenge. Virology 419:97-106.
  11. Briggs CM, Holder RC, Reid SD and Parks GD. 2011. Activation of human macrophages by bacterial components relieves the restriction on replication of an interferon-inducing parainfluenza virus 5 (PIV5) P/V mutant. Microbes and Infection. 13:359-368.
  12. Manuse MJ and Parks GD. 2010. TLR3-dependent upregulation of RIG-I leads to enhanced cytokine production from cells infected with the parainfluenza virus SV5. Virology 397: 231-241.
  13. Armilli S, Sharma SK, Yammani R, Reid SD, Parks GD, and Alexander-Miller MA. 2010. Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1. J. Leuk Biol. 87:977-88.
  14. Manuse MJ, Briggs CM, and Parks GD. 2010. Replication-Independent activation of human plasmacytoid dendritic cells by the paramyxovirus SV5 requires TLR7 and autophagy pathways. Virology 405:383-389.

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