Enveloped viruses are formed by a budding process that occurs following the assembly of viral components at cellular membranes. The late steps leading up to membrane fission and particle release appear to be accomplished in many cases through manipulation of host machinery that is recruited to virus assembly sites. As paramyxoviruses lack the same late domain sequences used by many other enveloped viruses, such as retroviruses, for host factor recruitment, the steps leading up to the release of paramyxovirus particles are poorly understood. Recently, we identified an alternative sequence, FPIV, within the matrix (M) protein of the paramyxovirus parainfluenza virus 5 (SV5) that can functionally substitute for the PTAP late domain of human immunodeficiency virus type 1 (HIV-1) for budding. Here, we propose experiments to further investigate mechanisms by which paramyxoviruses manipulate host machinery to facilitate virus budding.
Our first aim i s to investigate the role of the ubiquitin-proteasome pathway in SV5 budding by testing the possibility that SV5 M protein is a direct target for the attachment of ubiquitin molecules. We will attempt to prevent this ubiquitination from occurring through removal of lysine residues near the FPIV sequence of M protein.
Our second aim i s to define the subset of individual Class E proteins that is important for SV5 budding and that is recruited to SV5 assembly sites.
Our third aim i s to identify host proteins that bind to SV5 M protein, test the importance of M-interacting proteins for SV5 budding, and assess whether binding occurs in a way that is dependent on the FPIV sequence.
Our fourth aim i s to investigate the unique role of SV5 NP protein in the budding of virus-like particles. Relevance to public health: Paramyxoviruses are responsible for a wide range of diseases that affect both humans and animals, including measles and mumps. A better understanding of paramyxovirus budding will provide a foundation for future efforts towards the development of antiviral drugs that target this step of the virus lifecycle.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology - B Study Section (VIRB)
Program Officer
Cassetti, Cristina
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pennsylvania State University
Veterinary Sciences
Schools of Earth Sciences/Natur
University Park
United States
Zip Code
Ray, Greeshma; Schmitt, Phuong Tieu; Schmitt, Anthony P (2016) C-Terminal DxD-Containing Sequences within Paramyxovirus Nucleocapsid Proteins Determine Matrix Protein Compatibility and Can Direct Foreign Proteins into Budding Particles. J Virol 90:3650-60
Harrison, Megan S; Schmitt, Phuong Tieu; Pei, Zifei et al. (2012) Role of ubiquitin in parainfluenza virus 5 particle formation. J Virol 86:3474-85
Pei, Zifei; Harrison, Megan S; Schmitt, Anthony P (2011) Parainfluenza virus 5 m protein interaction with host protein 14-3-3 negatively affects virus particle formation. J Virol 85:2050-9
Schmitt, Phuong Tieu; Ray, Greeshma; Schmitt, Anthony P (2010) The C-terminal end of parainfluenza virus 5 NP protein is important for virus-like particle production and M-NP protein interaction. J Virol 84:12810-23
Pei, Zifei; Bai, Yuting; Schmitt, Anthony P (2010) PIV5 M protein interaction with host protein angiomotin-like 1. Virology 397:155-66
Harrison, Megan S; Sakaguchi, Takemasa; Schmitt, Anthony P (2010) Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol 42:1416-29
Li, Ming; Schmitt, Phuong Tieu; Li, Zhuo et al. (2009) Mumps virus matrix, fusion, and nucleocapsid proteins cooperate for efficient production of virus-like particles. J Virol 83:7261-72