Faculty Profile

Anthony V. Nicola

Anthony V. Nicola


Room: Bustad 315
Phone: 509-335-6003



  • BA: Drew University
  • PhD: University of Pennsylvania
  • Post-doctoral: Yale University and Swiss Federal Institute of Technology

Herpesviruses are a significant cause of morbidity and mortality in humans and animals worldwide. Herpes simplex virus (HSV) remains a major global pathogen causing oral and genital infections, blindness, encephalitis, and neonatal infections. The long-term goal of my laboratory is to understand the molecular processes that herpesviruses use to gain entry into host cells. HSV causes lifelong, latent infection for which there is no cure. A better understanding of how HSV interacts with the cell during the initial stages of infection will identify novel intervention strategies and antiviral drug targets. We utilize a combination of cellular, molecular, biochemical, and microscopic approaches to delineate the step-by-step itinerary of the incoming virus.

The long-held dogma that herpesviruses enter cells by fusion with the plasma membrane in a pH-independent manner was overturned when we identified a pH-dependent endocytic entry pathway for HSV into epithelial cells. It is now appreciated that herpesviruses utilize acid-dependent pathways in a cell-specific manner. Our current research focuses on the virus-cell interactions needed for two sequential steps in the initiation of infection: penetration of the genome-containing capsid into the cytoplasm and transport of the capsid to the nucleus, the site of herpesviral DNA replication. My lab has shown that to accomplish these steps, HSV engages the two distinct machineries of intracellular degradation: the low pH endosomal-lysosomal pathway and the 26S proteasome system.

cellular degradation machinery Model of the role of the cellular degradation machinery in the initiation of HSV infection. For illustration, nonendocytic (A) and endocytic (B) pathways are shown in a single cell. In neurons (A), the capsid penetrates directly at the plasma membrane. In mucosal epithelial cells (B), HSV is taken up by a lysosome-terminal endosomal pathway. The normal, low pH environment of an endosome serves as a cue for HSV to escape prior to lysosomal degradation. The mildly acidic pH of ~ 5.8 triggers conformational change in envelope glycoprotein B (gB), which is needed for membrane fusion and penetration of the capsid into the cytosol. Regardless of pathway (A, B), the penetrated capsid requires active proteasomes for transport to the nuclear envelope. The virion protein ICP0, which is present in the tegument layer, regulates the proteasome-dependent delivery of capsids.

Program Committee, American Society for Virology

Associate Editor, Virology Journal

Guest Associate Editor, PLoS Pathogens

Section Editor, Current Clinical Microbiology Reports

Lead Editor, Advances in Virology

Editorial Board, Journal of Virology

Select Publications
  • Tri Komala Sari, Katrina A Gianopulos, Anthony V Nicola (2020) Conformational Change in Herpes Simplex Virus Entry Glycoproteins Detected by Dot Blot Methods Mol Biol. ;2060:319-326. doi: 10.1007/978-1-4939-9814-2_18 PMID: 31617187 PMCID:
  • Weed DJ, Pritchard SM, Gonzalez F, Aguilar HC, Nicola AV (2017) Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry. J Virol. 91(5) PMID: 28003487 PMCID:
  • Nicola, A. V. (2016) Herpesvirus entry into host cells mediated by endosomal low pH. Traffic doi: 10.1111/tra.12408. PMID: 27126894 PMCID:
  • Stone, J. A., Nicola, A. V., Baum, L. G. and H. C. Aguilar (2016) Multiple novel functions of Henipavirus O-glycans: The first O-glycan functions identified in the Paramyxovirus family. PLoS Pathogens 12(2): e1005445 PMID: 26867212 PMCID: PMC4750917
  • Walker, E. B., Pritchard, S. M., Aguilar, H. C., and A. V. Nicola (2015) Polyethylene glycol-mediated fusion of herpes simplex virions with the plasma membrane of cells that support endocytic entry. Virology Journal 12:190 PMID: 26573723 PMCID: PMC4647588
  • Cunha, C. W., Taylor, K. E., Pritchard, S. M., Delboy, M. G., Komala Sari, T., Aguilar, H. C., Mossman, K. L. and A. V. Nicola (2015) A herpes simplex virus ICP0 deletion mutant does not express gC due to a mutation in the gC gene. PLoS ONE 10(7): e0131129 PMID: 26186447 PMCID: PMC4505948
  • Wudiri, G. A., Pritchard, S. M., Aguilar, H. C., Li, H., Liu, J., Gilk, S. D., and A. V. Nicola (2014) Molecular requirement for sterols in herpes simplex virus entry and infectivity. Journal of Virology 88: 13918-13922 PMID: 25231306 PMCID: PMC4248969
  • Barrow E, Nicola AV, Liu J (2013) Multiscale perspectives of virus entry via endocytosis. Virology Journal 10:177. doi: 10.1186/1743-422X-10-177. PMID: 23734580 PMCID: PMC3679726
  • Lu, X., Liu, Q., Benavides-Montano, J. A., Nicola, A. V., Aston, D. E., Rasco, B. and H. C. Aguilar (2013) Detection of receptor-induced glycoprotein conformational changes on enveloped virions using confocal micro-Raman spectroscopy. Journal of Virology 87: 3130-3142 PMID: 23283947 PMCID: PMC3592171
  • Pritchard, S. M., Cunha, C. W., and A. V. Nicola (2013) Analysis of herpes simplex virion tegument ICP4 derived from infected cells and ICP4-complementing cells. PLoS ONE 8 (8): e70889 PMID: 23940659 PMCID: PMC3735503
  • Komala Sari, T., Pritchard, S. M., Cunha, C. W., Wudiri, G. A., Laws, E. I., Aguilar, H. C., Taus, N. S., and A. V. Nicola (2013) Contributions of herpes simplex virus 1 envelope proteins to viral entry by endocytosis. Journal of Virology 87: 13922-13926 PMID: 24109213 PMCID: PMC3838226
  • Nicola AV, Aguilar HC, Mercer J, Ryckman B, Wiethoff CM. (2013) Virus entry by endocytosis. Advances in Virology 2013:469538. doi: 10.1155/2013/469538. Epub 2013 Apr 21. PMID: 23710180 PMCID: PMC3654661
  • Dollery SJ, Wright CC, Johnson DC, Nicola AV (2011) Low-pH-dependent changes in the conformation and oligomeric state of the prefusion form of herpes simplex virus glycoprotein B are separable from fusion activity. Journal of Virology 9964-73. doi: 10.1128/JVI.05291-11. Epub 2011 Aug 3 PMID: 21813610 PMCID: PMC3196434
  • Delboy, M. G. and A. V. Nicola (2011) A pre-immediate early role for tegument ICP0 in the proteasome-dependent entry of herpes simplex virus. Journal of Virology 85: 5910-5918 PMID: 21471243 PMCID: PMC3126318

List of Publications

2017-2021, Caroline Engle Distinguished Professor of Research on Infectious Diseases