Anthony Schmitt, Ph.D.

Anthony Schmitt, Ph.D.

  • Professor of Molecular Virology
  • Director, Pathobiology Graduate Program
208 AVBS Building
Shortlidge Road

University Park, PA 16802

Areas of Expertise

  • Virology
  • Infectious Disease
  • Viral Budding
  • Cellular Trafficking
  • Virus-like Particles
  • Zoonoses


  • Postdoctoral training in molecular virology with Dr. Robert A. Lamb, Northwestern University, Evanston, IL
  • PhD, Biological Chemistry with Dr. Kevin McEntee, UCLA School of Medicine
  • BS, Honors Biology, University of Illinois, Urbana

Graduate Programs


Assembly and Budding of Paramyxovirus Particles

Virus particles are vehicles that transmit infection from cell to cell and from host to host. For viruses that are membrane-enveloped, particles are formed by budding. Buds emerge from selected sites on cellular membranes, then pinch off and are released. Prior to budding, different viral components assemble together in a coordinated way and concentrate at budding sites. This assembly process allows for the release of particles that are likely to be infectious, as they are densely packed with viral proteins and contain viral genomes. My research group studies assembly and budding of the paramyxoviruses.  These enveloped RNA viruses include a number of important human and animal pathogens that impact human health and agriculture worldwide, including measles virus, mumps virus, Newcastle disease virus, and the zoonotic Nipah and Hendra viruses.

Paramyxovirus assembly

The Henipaviruses, Nipah virus and Hendra virus, are zoonotic paramyxoviruses of significant pandemic concern. Natural hosts for these viruses are pteropid fruit bats such as flying foxes that suffer no apparent illness from the infections but act as reservoirs, allowing spillover transmissions that can be deadly to other animals and to people. We have identified a number of host factors that bind to the Nipah and Hendra virus M proteins, and are working to develop new strategies for the inhibition of Henipavirus replication, by targeting M protein-host protein binding interfaces.  

Mumps virus has caused a resurgence of disease in developed countries in recent years.  Many of the molecular aspects of mumps virus replication, including mechanisms of virus assembly, remain poorly understood.  We have developed and optimized procedures that allow for efficient production of mumps virus-like particles (VLPs) in cultured mammalian cells.  The VLPs bud from transfected cells and resemble authentic virions when viewed with an electron microscope.  Interestingly, we found that cooperation among different mumps virus proteins was necessary for efficient VLP production.  We are currently investigating how mumps virus proteins are able to cooperate with one another during particle formation, and why such cooperation during VLP assembly is required for mumps virus, but not for many of the other paramyxoviruses.  In addition, we are examining the roles of host factors in mumps virus budding.

Parainfluenza virus 5 (PIV5) is a model paramyxovirus that is closely related to mumps virus.  A reverse genetics system has been established for PIV5, allowing recombinant viruses to be generated from cloned DNA.  By manipulating the infectious DNA clone, we are able to make targeted changes to the viral RNA genome and test what effects these changes have on virus assembly and budding.  Using this approach, we defined a region of the viral nucleocapsid (NP) protein that mediates interaction with the viral matrix (M) protein during virus assembly.  Recombinant viruses with defects in M-NP protein interaction acquired different types of adaptive mutations that provide new insights into mechanisms of virus spread.  We have also identified host factors that bind to the PIV5 M protein.  Angiomotin-like 1 (AMOTL1) and ubiquitin bind to PIV5 M protein and facilitate particle formation, while 14-3-3 protein binds to PIV5 M protein in a way that is detrimental to the virus assembly function of M protein.  We are currently working to understand the mechanisms by which these host factors influence PIV5 budding.

Technology Development

We are developing a new platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral M protein during VLP assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The cargo-loaded VLPs contain the viral attachment and fusion glycoproteins, and so are capable of delivering their contents directly to the cytoplasms of target cells. We are now working to apply this technology towards delivery of therapeutic proteins including CRISPR enzymes.

Selected Publications

Panthi S, Schmitt PT, Lorenz FJ, Stanfield BA, Schmitt AP. Paramyxovirus-Like Particles as Protein Delivery Vehicles. J Virol, 95:e0103021, 2021.

Rheinemann L, Downhour DM, Bredbenner K, Mercenne G, Davenport KA, Schmitt PT, Necessary CR, McCullough J, Schmitt AP, Simon SM, Sundquist WI, Elde NC. RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis. Cell, 184:5419–5431.e16, 2021.

Ray, G., Schmitt, P.T., and Schmitt, A.P. Angiomotin-Like 1 Links Paramyxovirus M Proteins to NEDD4 Family Ubiquitin Ligases. Viruses, 11, 128, 2019.

Carmichael JC, Yokota H, Craven RC, Schmitt A, Wills JW.  The HSV-1 mechanisms of cell-to-cell spread and fusion are critically dependent on host PTP1B. PLoS Pathog 14:e1007054, 2018.

Cifuentes-Muñoz, Sun, W., Ray, G., Schmitt, P.T., Webb, S., Gibson, K., Dutch, R.E., and Schmitt, A.P.  Mutations in the transmembrane domain and cytoplasmic tail of Hendra virus fusion protein disrupt virus-like particle assembly.  J Virol. 91, 2017. doi: 10.1128/JVI.00152-17.

Ray, G., Schmitt, P. T., and Schmitt, A. P.  C-terminal DxD-containing sequences within paramyxovirus nucleocapsid proteins determine matrix protein compatibility, and can direct foreign proteins into budding particles. J Virol. 90, 3650-3660, 2016.

Sun, W., McCrory, T. S., Khaw, W. Y., Petzing, S., Myers, T., and Schmitt, A. P. Matrix Proteins of Nipah and Hendra Viruses Interact with Beta Subunits of AP-3 Complexes. J Virol. 88, 13099-13110, 2014.

El Najjar, F., Schmitt, A. P., and Dutch, R. E. Paramyxovirus Glycoprotein Incorporation, Assembly and Budding: A Three Way Dance for Infectious Particle Production. Viruses. 6, 3019-3054, 2014.

Johnson, J. B., Schmitt, A. P., and Parks, G. D. Point mutations in the paramyxovirus F protein that enhance fusion activity shift the mechanism of complement-mediated virus neutralization. J Virol. 87, 9250-9259, 2013.

Oka, T., Schmitt, A. P., and Sudol, M. Opposing roles of angiomotin-like-1 and zona occludens-2 on pro-apoptotic functions of YAP. Oncogene. 31, 128-134, 2012.

Harrison, M. S., Schmitt, P. T., Pei, Z., and Schmitt, A. P. Role of ubiquitin in PIV5 particle formation. J Virol. 86, 3474-3485, 2012.

Pei, Z., Harrison, M. S., and Schmitt, A. P. PIV5 M protein interaction with host protein 14-3-3 negatively affects virus particle formation. J Virol. 85, 2050-2059, 2011.

Schmitt, P. T., Ray, G., and Schmitt, A. P. The C-terminal end of PIV5 NP protein is important for virus-like particle production and M-NP protein interaction. J Virol. 84, 12810-12823, 2010.

Pei, Z., Bai, Y., and Schmitt, A. P. PIV5 M protein interaction with host protein angiomotin-like 1. Virology, 397, 155-166, 2010. 

Harrison, M. S., Sakaguchi, T., and Schmitt, A. P. Paramyxovirus assembly and budding: building particles that transmit infections. Intl J Biochem Cell Biol. 42, 1416-1429, 2010.

Li, M., Schmitt, P. T., Li, Z., McCrory, T. S., He, B., and Schmitt, A. P. Mumps virus matrix, fusion, and nucleocapsid proteins cooperate for efficient production of virus-like particles. J Virol.  83, 7261-7272, 2009.

Schmitt, A. P., Leser, G. P., Morita, E., Sundquist, W. I., and Lamb, R. A. Evidence for a new viral late domain core sequence, FPIV, necessary for budding of a paramyxovirus. J Virol. 79, 2988-2997, 2005. 

Schmitt, A. P., and  Lamb, R. A. Escaping from the cell:  Assembly and budding of negative-strand RNA viruses. Curr Top Microbiol Immunol. 283, 145-196, 2004. 

Schmitt, A. P., Leser, G. P., Waning, D. L., and Lamb, R .A. Requirements for budding of paramyxovirus simian virus 5 virus-like particles. J Virol. 76, 3952-3964, 2002. 

Schmitt, A. P., He, B., and Lamb, R. A. Involvement of the cytoplasmic domain of the hemagglutinin-neuraminidase protein in assembly of the paramyxovirus simian virus 5. J Virol. 73, 8703-8712, 1999. 


Santosh Panthi - Paramyxovirus M-NP interactions

Dr. Phuong Schmitt - Assembly and budding of paramyxoviruses

Caroline Ho - Nipah virus particle assembly

Luke May - Nipah virus particle assembly

Jonathan Webber - Nipah virus particle assembly

Schmitt Lab 2019

Prospective Lab Members

Interested in conducting your PhD research in this laboratory?  Apply to Penn State's Pathobiology graduate program.