Education

A.B. Cornell University, 1972
Ph.D. Stanford University, 1979

Research Interests

The virus envelope glycoprotein orchestrates entry of the virus into its target cell by mediating attachment to cell-surface receptors and fusion of the virus and cell membranes. As such, these glycoproteins provide fertile ground for study towards the development of antiviral agents and vaccines. My laboratory is interested in cellular, molecular, and structural aspects of virus assembly and entry.

The recent focus of my lab has been on the envelope glycoprotein (GPC) of the Arenaviruses, a little-studied family of rodent-borne viruses responsible for hemorrhagic fevers worldwide (Lassa fever in Africa, and South American hemorrhagic fevers in the New World). Over the past several years, we have characterized the unusual GPC complex. In addition to the receptor-binding and transmembrane fusion subunits common to all Class I envelope glycoproteins, GPC retains a cleaved and stable signal peptide (SSP) as an essential element. On the cytoplasmic face of GPC, SSP likely forms an intersubunit zinc-finger structure with the transmembrane subunit and functions in intracellular transport of GPC to the cell surface, and in virion assembly. The ectodomain of SSP interacts with the ectodomain of the transmembrane fusion subunit to modulate low pH-induced activation of membrane fusion, which takes place in the maturing endosome of the cell. This interaction provides the basis for fusion inhibition by structurally diverse small-molecule antiviral compounds and may be involved in vaccine attenuation. Genetic and structural studies are underway to better understand this critical viral target for antiviral and vaccine development.

Selected Publications

York J, Nunberg JH. Epistastic Interactions within the Junín Virus Envelope Glycoprotein Complex Provide an Evolutionary Barrier to Reversion in the Live-Attenuated Candid#1 Vaccine. (2018) J Virol. 92:1-14.

Zeltina A, Krumm SA, Sahin M, Struwe WB, Harlos K, Nunberg JH, Crispin M, Pinschewer DD, Doores KJ, Bowden TA. (2017) Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization. Proc Natl Acad Sci U S A. 114:7031-7036.

York J, Nunberg JH. Myristoylation of the Arenavirus Envelope Glycoprotein Stable Signal Peptide Is Critical for Membrane Fusion but Dispensable for Virion  Morphogenesis. (2016) J Virol.  90:8341-50.

Shankar S, Whitby LR, Casquilho-Gray HE, York J, Boger DL, Nunberg JH. (2016) Small-Molecule Fusion Inhibitors Bind the pH-Sensing Stable Signal Peptide-GP2 Subunit Interface of the Lassa Virus Envelope Glycoprotein. J Virol. 90:6799-807.

Baird NL, York J, Nunberg JH. Arenavirus infection induces discrete cytosolic  structures for RNA replication. (2012) J Virol. 86:11301-10.

Thomas CJ, Shankar S, Casquilho-Gray HE, York J, Sprang SR, Nunberg JH. (2012) Biochemical reconstitution of hemorrhagic-fever arenavirus envelope glycoprotein-mediated membrane fusion. PLoS One. 7:e51114.

York J, Dai D, Amberg SM, Nunberg JH. (2008) pH-induced activation of arenavirus membrane fusion is antagonized by small-molecule inhibitors. J Virol. 82:10932-9.

Professional Experience

Dr. Nunberg has over 20 years experience in the biotechnology (Cetus Corporation, Genentech Inc.) and pharmaceutical (Merck Research Labs) industries prior to founding the Montana Biotechnology Center at UM. Dr. Nunberg supervises the core BSL3 laboratory at UM.