Susan R. Weiss

faculty photo
Professor of Microbiology
Department: Microbiology

Contact information
203A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076
Office: (215) 898-8013
Fax: (215) 573-4858
Lab: 215-898-3551
Graduate Group Affiliations
B.A. (Biology)
Brandeis University, 1971.
Ph.D. (Microbiology and Molecular Genetics)
Harvard University, 1975.
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Description of Research Expertise

Research Interests
- Murine coronavirus pathogenesis, central nervous system, liver and lung
- Murine coronavirus antagonism of the OAS-RNase L pathway
- Organ specific virus- host interactions
- Role of inflammasome related cytokines in murine coronavirus acute disease and chrinic demyelination

Key words: murine coronavirus, human respiratory coronavirus, viral pathogenesis, interferon antagonist.

Description of Research

Susan Weiss, Ph.D.

Professor of Microbiology

Office Address:
University of Pennsylvania School of Medicine
203 A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076

TEL 215-898-8013
LAB 215-898-3551
FAX 215-573-4858


My lab studies coronavirus pathogenesis. We use murine coronavirus, mouse hepatitis virus (MHV) infection of mice as a model system for the study of: 1) acute viral encephalitis; 2) chronic demyelinating diseases such as Multiple Sclerosis and 3) virus-induced hepatitis. We have the important tools of a well-developed animal model system and two reverse genetic systems with which to manipulate the viral genome. Human coronaviruses are primarily respiratory viruses, and include the common cold viruses OC43 and 229E as well as the emerging viruses MERS and SARs that cause severe and life threatening diseases. We are beginning to study human coronavirus interactions with respiratory tract cells. Our long-term goal is to elucidate the viral and cellular determinants of coronavirus tropism and pathogenesis in the brain, the liver and the lung. Much of our current work focuses on coronavirus-encoded antagonists of type I interferon, specifically virus-encoded phosphodiesterase that antagonize the OAS-RNase L pathway. Another direction in our lab is the study of the role of inflammasome related cytokines in viral clearance as well as both acute and chronic MHV induced disease.

Currently we are carrying out the following studies:

1. Virus-encoded phosphodiesterases (PDE), that act as type I interferon antagonists. The MHV ns2 gene encodes a phosphodiesterase activity that specifically cleaves 2-5A, the activator of Ribonuclease (RNase) L, a potent antiviral response induced by type I interferon and infection. Homologous proteins with RNase L antagonist activates are also expressed by some other coronaviruses, toroviruses, other members of the coronavirus superfamily as well as type A rotaviruses, that cause severe gastrointestinal infections of children. Activation of RNase is cell type specific and most most robust in myeloid cells and antagonism of RNase L is required for the induction of hepatitis by MHV. We are currently investigating the mechanisms underlying activation of this pathway and antagonism by virus induced phosphodiesterase and their role in pathogenesis.

2. Human coronaviruses and RNase L antagonism. A group of other group 2a Betacorovaviruses encode ns2 homologs that we have recently found to have phosphodiesterase activity. We are characterizing these PDEs now and beginning to investigate a possible role for RNase L antagonism in the respiratory tract, the major target of most human coronaviruses including the lethal, emerging pathogen SARS and MERS.

2. Inflammasome associated cytokines and MHV acute and chronic disease pathogenesis. We are investigating the roles of the two inflammasome related cytokines IL-1 an IL-18 in coronavirus pathogenesis. This includes understanding their roles in protection against and contribution to acute encephalitis and hepatitis and in addition a possible role in the chronic demyelinating disease.

3. Role of receptor in MHV entry, spread and pathogenesis. The only known receptor for MHV is the carcinoembryonic antigen protein, CEACAM 1. However, the highly neurovirulent MHV-JHM strain spreads cell to cell in the absence of the expression of this receptor. Using transgenic CEACAM 1 deficient mice (ceacam 1a -/-), we have found that JHM can replicate and cause CNS disease and mortality in the absence of viral receptor. We are using a selection of MHV mutants and tropism variants in combination with primary cells derived from wild type and ceacam 1a-/- mice to elucidate the mechanism of viral neuron to neuron spread and the role of receptor independent spread in disease. We also plan to discover alternate receptors used by MHV in the absence of ceacam1a.

Rotation Projects

1. Coronavirus RNase L antagonists: Investigation of the mechanism by which MHV ns2 as well as human coronavirus ns2 homologs inhibit the oligoadenylate synthetase (OAS)-ribonuclease (RNase) L interferon stimulated anti-viral pathway. This includes understanding the contributions of host OAS and RNase L gene expression, host interferon response as well as virus encoded phosphodiesterase in the activation and antagonism of RNase L. Projects also include investigation of activation of the OAS-RNase L pathway in myeloid cells versus other cell types and how this impacts on pathogenesis. These projects involve studies of virus in primary cell types as well as in vivo experiments in mice and involve carrying out a wide variety of techniques, including viral pathogenesis, cell culture, cloning, in vitro protein expression and real time qPCR.

2. Mechanisms of MHV neurovirulence. Investigation of the roles of IL-1 and IL-18 in MHV pathogenesis and clearance (comparing effects in the brain and liver) as well as virus induced demyelination. This includes comparison of viral replication and clearance during infection of IL-1R and IL-18R knockout mice with C57/Bl6 wild type mice and the mechanisms underlying difference between pathgoenesis of wild type an knockout mice. This project includes cell culture, infections of mice, isolation of immune cells, flow cytometry as well as Western blots.

Lab personnel:

Dillon Birdwell- Graduate Student
Ruth Elliott - Research Specialist
Yize (Henry) Li- Postdoctoral Researcher
Judith Phillips- Research Associate
Sasha Stone- Undergraduate Student
Joshua Thornbrough- Postdoctoral Researcher
Zachary Zalinger- Graduate student

Description of Itmat Expertise

viral pathogenesis

Selected Publications

Zhang Rong, Jha Babal K, Ogden Kristen M, Dong Beihua, Zhao Ling, Elliott Ruth, Patton John T, Silverman Robert H, Weiss Susan R: Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America 110(32): 13114-9, Aug 2013.

Zhao Ling, Birdwell L Dillon, Wu Ashley, Elliott Ruth, Rose Kristine M, Phillips Judith M, Li Yize, Grinspan Judith, Silverman Robert H, Weiss Susan R: Cell-type-specific activation of the oligoadenylate synthetase-RNase L pathway by a murine coronavirus. Journal of virology 87(15): 8408-18, Aug 2013.

Adedeji Adeyemi O, Severson William, Jonsson Colleen, Singh Kamalendra, Weiss Susan R, Sarafianos Stefan G: Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. Journal of virology 87(14): 8017-28, Jul 2013.

Elliott Ruth, Li Fan, Dragomir Isabelle, Chua Ming Ming W, Gregory Brian D, Weiss Susan R: Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice. PloS one 8(9): e75346, 2013.

Adedeji Adeyemi O, Singh Kamalendra, Calcaterra Nicholas E, Dediego Marta L, Enjuanes Luis, Weiss Susan, Sarafianos Stefan G: SARS-CoV Replication Inhibitor that Interferes with the Nucleic acid Unwinding of the Viral Helicase. Antimicrobial agents and chemotherapy 56(9): 4718-28, Jun 2012.

Zhao Ling, Jha Babal K, Wu Ashley, Elliott Ruth, Ziebuhr John, Gorbalenya Alexander E, Silverman Robert H, Weiss Susan R: Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology. Cell host & microbe 11(6): 607-16, Jun 2012.

Phillips Judith M, Kuo I-Ting, Richardson Chelsea, Weiss Susan R: A novel full-length isoform of murine pregnancy-specific glycoprotein 16 (psg16) is expressed in the brain but does not mediate murine coronavirus (MHV) entry. Journal of neurovirology 18(2): 138-43, Apr 2012.

Adedeji Adeyemi O, Marchand Bruno, Te Velthuis Aartjan J W, Snijder Eric J, Weiss Susan, Eoff Robert L, Singh Kamalendra, Sarafianos Stefan G: Mechanism of nucleic acid unwinding by SARS-CoV helicase. PloS one 7(5): e36521, 2012.

Zhao Ling, Rose Kristine M, Elliott Ruth, Van Rooijen Nico, Weiss Susan R: Cell-type-specific type I interferon antagonism influences organ tropism of murine coronavirus. Journal of virology 85(19): 10058-68, Oct 2011.

Hollidge Bradley S, Weiss Susan R, Soldan Samantha S: The role of interferon antagonist, non-structural proteins in the pathogenesis and emergence of arboviruses. Viruses 3(6): 629-58, Jun 2011.

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Last updated: 01/31/2014
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