College of Veterinary Medicine

Veterinary Microbiology and Pathology

Anthony V. Nicola, Ph.D.

Anthony NicolaAnthony V. Nicola, Ph.D.
Assistant Professor of Virology
509-335-6003 (tel)

B.A., Drew University
Ph.D., 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.

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.

Recent publications

Dollery, S. J., M. G. Delboy, and A. V. Nicola. 2010. Low pH-induced conformational change in herpes simplex virus glycoprotein B. Journal of Virology 84: 3759-3766.

Delboy, M.G., C. R. Siekavizza-Robles and A. V. Nicola. 2010. Herpes simplex virus tegument ICP0 is capsid-associated and its E3 ubiquitin ligase domain is important for incorporation into virions. Journal of Virology 84: 1637-1640.

Siekavizza-Robles, C. R., S. J. Dollery and A. V. Nicola. 2010. Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH. Virology Journal 7: 586.

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. Featured in JVI Spotlight.

Dollery, S. J., C. C. Wright, D. C. Johnson and A. V. Nicola. 2011. Low pH-dependent changes in the conformation and oligomeric state of the pre-fusion form of herpes simplex virus glycoprotein B are separable from fusion activity. Journal of Virology 85: 9964-9973.

All publications
Last Edited: Sep 29, 2011 1:32 PM   

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