Paul Ahlquist

About

Paul Ahlquist is a professor in the Department of Plant Pathology at the University of Wisconsin-Madison. He holds a Ph.D. in Biophysics from the University of Wisconsin-Madison. His research focuses on studying the novel, RNA-based pathways and virus-host interactions underlying replication, gene expression, and evolution by positive-strand RNA viruses, which include many important human pathogens such as hepatitis C virus and the SARS coronavirus. His work integrates molecular genetics, genomics, biochemistry, and cell biology to address fundamental questions in virus replication and virus-cell interactions. Ahlquist's research has led to significant discoveries, including the identification of structural and functional parallels among the replication complexes of different virus classes, implying a functional and evolutionary unification within virology. He has also identified the first higher eukaryotic viruses capable of directing genome replication, gene expression, and virion assembly in the genetically tractable yeast Saccharomyces cerevisiae. Using yeast genetics and genomics, his studies aim to identify host genes required for viral RNA replication and to understand how these genes function with virus-encoded factors to facilitate viral processes.

Research topics

• Molecular biology
• Virology
• Biology
• Cell biology
• Biochemistry

Selected publications

• Subdomain cryo-EM structure of nodaviral replication protein A crown complex provides mechanistic insights into RNA genome replication

  Proceedings of the National Academy of Sciences · 2020-07-20 · 46 citations

  articleOpen accessSenior author

  For positive-strand RNA [(+)RNA] viruses, the major target for antiviral therapies is genomic RNA replication, which occurs at poorly understood membrane-bound viral RNA replication complexes. Recent cryoelectron microscopy (cryo-EM) of nodavirus RNA replication complexes revealed that the viral double-stranded RNA replication template is coiled inside a 30- to 90-nm invagination of the outer mitochondrial membrane, whose necked aperture to the cytoplasm is gated by a 12-fold symmetric, 35-nm di…

  PublisherOA PDFDOI

• Positive-strand RNA virus genome replication organelles: structure, assembly, control

  Trends in Genetics · 2024-05-08 · 36 citations

  reviewOpen accessSenior authorCorresponding

  Positive-strand RNA [(+)RNA] viruses include pandemic SARS-CoV-2, tumor-inducing hepatitis C virus, debilitating chikungunya virus (CHIKV), lethal encephalitis viruses, and many other major pathogens. (+)RNA viruses replicate their RNA genomes in virus-induced replication organelles (ROs) that also evolve new viral species and variants by recombination and mutation and are crucial virus control targets. Recent cryo-electron microscopy (cryo-EM) reveals that viral RNA replication proteins form st…

  PublisherOA PDFDOI

• Nodavirus RNA replication crown architecture reveals proto-crown precursor and viral protein A conformational switching

  Proceedings of the National Academy of Sciences · 2023-01-24 · 21 citations

  articleOpen accessSenior author

  Positive-strand RNA viruses replicate their genomes in virus-induced membrane vesicles, and the resulting RNA replication complexes are a major target for virus control. Nodavirus studies first revealed viral RNA replication proteins forming a 12-fold symmetric "crown" at the vesicle opening to the cytosol, an arrangement recently confirmed to extend to distantly related alphaviruses. Using cryoelectron microscopy (cryo-EM), we show that mature nodavirus crowns comprise two stacked 12-mer rings…

  PublisherOA PDFDOI

• Multifunctional Protein A Is the Only Viral Protein Required for Nodavirus RNA Replication Crown Formation

  Viruses · 2022-12-03 · 10 citations

  articleOpen accessSenior authorCorresponding

  Positive-strand RNA virus RNA genome replication occurs in membrane-associated RNA replication complexes (RCs). Nodavirus RCs are outer mitochondrial membrane invaginations whose necked openings to the cytosol are “crowned” by a 12-fold symmetrical proteinaceous ring that functions as the main engine of RNA replication. Similar protein crowns recently visualized at the openings of alphavirus and coronavirus RCs highlight their broad conservation and functional importance. Using cryo-EM tomograph…

  PublisherOA PDFDOI

• HIV-1 virological synapse formation enhances infection spread by dysregulating Aurora Kinase B

  PLoS Pathogens · 2023-07-17 · 9 citations

  articleOpen accessSenior authorCorresponding

  HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between HIV-1 envelope proteins (Env) on the surface of infected cells and CD4 receptors on uninfected target cells. Env-CD4 interactions bring the infected and uninfected cellular membranes into close proximity and induce transport of viral and cellular factors to the VS for efficient virion assembly and HIV-1 transmission. Using novel, cell-specific stable isotope labeling an…

  PublisherOA PDFDOI

Recent grants

• Core C - Virus/Vector

  NIH · $113.8M · 1997–2029

• NIH Grant R01CA097944

  NIH · $1.4M · 2007

• NIH Grant R01GM035072

  NIH · $3.3M · 2011

Frequent coauthors

• Hong Zhan

  University of Wisconsin–Madison

  161 shared

• Nuruddin Unchwaniwala

  161 shared

• Janice Pennington

  University of Wisconsin–Madison

  160 shared

• Masaki Nishikiori

  Morgridge Institute for Research

  157 shared

• Johan A. den Boon

  Morgridge Institute for Research

  137 shared

• Irina Novikova

  Pacific Northwest National Laboratory

  129 shared

• Nancy Meyer

  Oregon Health & Science University

  89 shared

• Michael Janda

  68 shared

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