Paul F. Bates, PhD

faculty photo
Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
303A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
Office: (215) 573-3509
B.S. (Biochemistry)
Pennsylvania State University, 1979.
Ph.D. (Biochemistry)
Michigan State University, 1985.
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Description of Research Expertise

Research Interests
The Bates lab is interested in the interactions between viruses and their host cells. We use a combination of molecular, cell biological, and genetic tools to understand how viruses invade host cells and evade host defenses with recent emphasis on emerging viral pathogens.

Key words: Virus entry, glycoproteins, Tetherin, ebolavirus, hantavirus, SARS, retrovirus

Description of Research
Generally, research in the Bates lab focuses on viral glycoproteins and host factors that facilitate infection. Although we work with a number of different viral systems, current projects concentrate on several pathogenic viruses including filoviruses (ebolavirus and Marburgvirus) and bunyaviruses (Hantaan, Andes, Sin Nombre, La Crosse). We recently initiated research on the intrinsic antiviral factor, Tetherin, that we showed is a broadly acting antiviral factor capable of activating NFkB. Current research is examining whether Tetherin is a new innate immune pattern recognition receptor.

Interrogation of insertionally mutagenized haploid cells is a powerful technology to identify genes important for a specific function. The recent availability of haploid mammalian cells makes possible the use of this technology to identify host factors that interact with viruses and promote infection. We have developed a gene-trap lentiviral vector that act as an insertional mutagen and produced a library of >200 million haploid human cells bearing insertions and are interrogating this library by employing novel replication-competent, recombinant viruses. Cells resistant to infection by these recombinant viruses contain inactivating mutations in host factors needed for infection that can be readily identified using massively parallel deep sequencing technology. Currently our focus for this line of research are members of the Bunyaviridae family. Bunyaviruses include many important human pathogens such as Crimean Congo Hemorrhagic Fever Virus, Hantaan Virus, Rift Valley Fever Virus, Andes virus and Sin Nombre Virus.

Ebolavirus infection is associated with a high mortality rate and there are no effective treatments for Ebola infection. The ongoing research in my lab addresses three important questions regarding ebolavirus glycoprotein (GP) interactions with the host. First, what are the cellular factors required for ebolavirus entry? Second, how does ebolavirus GP antagonize the function of the cellular antiviral factor Tetherin? Third, what is the impact of ebolavirus GP's novel mechanism of surface protein down-modulation via steric occlusion on immune recognition? Answers to these questions will provide important new information about how ebolavirus interacts with the host. In addition, these studies are likely to suggest new therapeutic or prophylactic strategies to combat ebolavirus infection. Finally, the proposed steric shielding model for surface protein down-regulation by ebolavirus represents a novel mechanism for a viral glycoprotein affecting host cell function and may also be informative for cellular mucin proteins involved in metastatic cancer.

Mammalian cells employ numerous innate cellular mechanisms to inhibit viral replication and spread. Tetherin, also known as Bst2 or CD317, is an interferon-induced, cellular response factor that was initially found to block release of HIV-1 and other retroviruses from infected cells. Our lab demonstrated that Tetherin functions as a broadly acting antiviral factor by showing that both human and murine Tetherin potently inhibit the release of the filovirus, ebolavirus, from the surface of cells. Moreover we found that the ebolavirus glycoprotein (GP) antagonized the antiviral effect of human and murine Tetherin and facilitated viral budding. However, the mechanism by which ebolavirus impedes Tetherin function is unknown and is one of the areas under active investigation in our lab. Additionally, we recently identified two species of the Tetherin protein generated by alternative translation initiation that display dramatically different biologic activities. Although both protein isoforms act as antiviral factors to retain budding virions, the shorter Tetherin isoform is significantly more resistant to HIV Vpu-mediated antagonism and degradation. Consequently s-Tetherin is a very potent HIV-1 restriction factor. By contrast, that the longer isoform is highly susceptible to Vpu mediated antagonism. Importantly, we determined that l-Tetherin (but not s-Tetherin) activates the immune regulatory transcription factor NF-κB. Current research is investigating the importance of these isoforms as potential pattern recognition receptors.

Selected Publications

Cocka Luis J, Bates Paul: Identification of alternatively translated Tetherin isoforms with differing antiviral and signaling activities. PLoS pathogens 8(9): e1002931, Sep 2012.

Haines Kathleen M, Vande Burgt Nathan H, Francica Joseph R, Kaletsky Rachel L, Bates Paul: Chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for NPC1 expression. Virology 432(1): 20-8, Oct 2012.

Francica Joseph R, Varela-Rohena Angel, Medvec Andrew, Plesa Gabriela, Riley James L, Bates Paul: Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS pathogens 6(9): e1001098, 2010.

Kaletsky Rachel L, Francica Joseph R, Agrawal-Gamse Caroline, Bates Paul: Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proceedings of the National Academy of Sciences of the United States of America 106(8): 2886-91, Feb 2009.

Francica Joseph R, Matukonis Meghan K, Bates Paul: Requirements for cell rounding and surface protein down-regulation by Ebola virus glycoprotein. Virology 383(2): 237-47, Jan 2009.

Kaletsky Rachel L, Simmons Graham, Bates Paul: Proteolysis of the Ebola virus glycoproteins enhances virus binding and infectivity. Journal of virology 81(24): 13378-84, Dec 2007.

Chai Ning, Bates Paul: Na+/H+ exchanger type 1 is a receptor for pathogenic subgroup J avian leukosis virus. Proceedings of the National Academy of Sciences of the United States of America 103(14): 5531-6, Apr 2006.

Simmons Graham, Gosalia Dhaval N, Rennekamp Andrew J, Reeves Jacqueline D, Diamond Scott L, Bates Paul: Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proceedings of the National Academy of Sciences of the United States of America 102(33): 11876-81, Aug 2005.

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Last updated: 02/23/2023
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