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Paul G. Ahlquist, Ph.D.

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P. Ahlquist photo Paul J. Kaesberg Professor of Oncology and Molecular Virology
Investigator, Howard Hughes Medical Institute

B.S., 1976, Physics, Iowa State University
Ph.D., 1981, Biophysics, University of Wisconsin-Madison

Office: 841A Bock Laboratories
Telephone: Office - (608) 263-5916; Lab - (608) 261-1148/5-9743
Email: ahlquist@wisc.edu

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Research Interests: Molecular mechanisms of viral replication, host interactions and oncogenesis.

Research Description: We are studying the novel, RNA-based pathways and virus-host interactions underlying replication, gene expression and evolution by positive-strand RNA viruses, the largest class of viruses. Positive strand RNA viruses include many important human pathogens such as hepatitis C virus, which chronically infects nearly 3% of the world population, causing progressive liver damage and liver cancer, and the new SARS coronavirus. We are also studying selected replication processes of a reverse-transcribing virus, hepatitis B virus, which is also a major human tumor virus. Our studies integrate molecular genetics, genomics, biochemistry and cell biology to address fundamental questions in virus replication and virus-cell interactions.

Viruses are divided into six distinct classes differing in the type of nucleic acid in the virus particle and its replication pathways. Recently, we discovered multiple, detailed structural and functional parallels among the replication complexes of three of these six virus classes: positive-strand RNA viruses, retroviruses and dsRNA viruses. These results imply a significant functional and evolutionary unification within virology, and have opened the door to many exciting new experimental questions and approaches that we are now pursuing.

We also have identified the first higher eukaryotic viruses that can direct genome replication, gene expression and virion assembly in the genetically tractable yeast Saccharomyces cerevisiae. Using yeast genetics and genomics, we are identifying a growing number of host genes required for viral RNA replication and are studying how these function with virus-encoded helicase- and polymerase-like replication factors and diverse cis-acting viral RNA signals to direct assembly and function of the membrane-bound viral genome replication complexes and other processes.

Selected recent publications

Chasman, D., Gancarz, B., Hao, L., Ferris, M., Ahlquist, P., and Craven, M.  Inferring Host Gene Subnetworks Involved in Viral Replication.  PLoS Comput. Biol., 10(5):e1003626, 2014.

Hao, L., Lindenbach, B., Wang, X., Dye, B., Kushner, D., He, Q., Newton, M., and Ahlquist, P.  Genome-Wide Analysis of Host Factors in Nodavirus RNA Replication.  PLoS One, 9(4):e95799, 2014.

Wang, L., Zhao, Z., Meyer, M. B., Saha, S., Yu, M., Guo, A., Wisinski, K. B., Huang, W., Cai, W., Pike, J. W., Yuan, M., Ahlquist, P., and Xu, W.  CARM1 Methylates Chromatin Remodeling Factor BAF155 to Enhance Tumor Progression and Metastasis.  Cancer Cell, 25(1):  21-36, 2014.

Bruce, J. W., Reddington, R., Mathieu, E., Bracken, M., Young, J. A. T., and Ahlquist, P.  ZASC1 Stimulates HIV-1 Transcription Elongation by Recruiting P-TEFb and TAT to the LTR Promoter.  PLoS Pathog., 9(10): e1003712, 2013.

Giménez-Barcons, M., Alves-Rodrigues, I., Jungfleisch, J., Van Wynsberghe, P. M., Ahlquist, P., and Díez, J.  The Cellular Decapping Activators LSm1, Pat1, and Dhh1 Control the Ratio of Subgenomic to Genomic Flock House Virus RNAs.  J. Virol., 87(11): 6192-6200, 2013.

Hao, L., He, Q., Wang, Z., Craven, M., Newton, M. A., and Ahlquist, P.  Limited Agreement of Independent RNAi Screens for Virus-Required Host Genes Owes More to False-Negative than False-Positive Factors.  PLoS Comput. Biol., 9(9):e1003235, 2013.

Seidel, S., Bruce, J., Leblanc, M., Lee, K.-F., Fan, H., Ahlquist, P., and Young, J. A. T.  ZASC1 Knockout Mice Exhibit an Early Bone Marrow-Specific Defect in Murine Leukemia Virus Replication.  Virol. J., 10(1): 130, 2013.

Zhao, Z., Wang, L., Wen, Z., Ayaz-guner, S., Wang, Y., Ahlquist, P., and Xu, W.  Systematic Analyses of the Cytotoxic Effects of Compound 11a, a Putative Synthetic Agonist of Photoreceptor-Specific Nuclear Receptor (PNR), in Cancer Cell Lines.  PLoS One, 8(9):e75198, 2013.

Diaz, A., and Ahlquist, P.  Role of Host Reticulon Proteins in Rearranging Membranes for Positive-Strand RNA Virus Replication.  Curr. Opin. Microbiol., 15: 519-524, 2012.

Diaz, A., Gallei, A., and Ahlquist, P.  Bromovirus RNA Replication Compartment Formation Requires Concerted Action of 1a’s Self-Interacting RNA Capping and Helicase Domains.  J. Virol., 86:  821-834, 2012.

Huang, H.-S., Pyeon, D., Pearce, S. M., Lank, S. M., Griffin, L. M., Ahlquist, P., and Lambert, P. F.  Novel Antivirals Inhibit Early Steps in HPV Infection.  Antiviral Res., 93:  280-287, 2012.

Wen, Z., Pyeon, D., Wang, Y., Lambert, P., Xu, W., and Ahlquist, P.  Orphan Nuclear Receptor PNR/NR2E3 Stimulates p53 Functions by Enhancing p53 Acetylation.  Mol. Cell. Biol., 32:  26-35, 2012.

Zhang, J., Diaz, A., Mao, L., Ahlquist, P., and Wang, X.  Host Acyl Coenzyme A Binding Protein Regulates Replication Complex Assembly and Activity of a Positive-Strand RNA Virus.  J. Virol., 86: 5110-5121, 2012.

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