Description of Research Expertise

Research Interests
- Murine coronavirus pathogenesis, central nervous system, liver and lung
- Murine coronavirus antagonism of the OAS-RNase L pathway
- Initiation of a T cell response in the central nervous system
- Organ specific virus- host interactions


Key words: murine coronavirus, SARS associated coronavirus, viral pathogenesis.

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
weisssr@mail.med.upenn.edu

RESEARCH SUMMARY

My lab is involved in the study of pathogenesis of coronaviruses. We have been studying the murine coronavirus, mouse hepatitis virus (MHV) for many years. The murine coronavirus virus (MHV) infection of rodents with MHV provides a model system for the study of: 1) acute viral infection of the central nervous system (CNS) and both innate and acquired immune response to this infection; 2) a chronic persistent infection which proceeds in the presence of virus specific CD8T cells and provides one of the best models for the human demyelinating diseases such as Multiple Sclerosis and 3) virus-induced hepatitis. Our long term goal is to elucidate the viral and cellular determinants of tropism and pathogenesis in both the brain and the liver. In order to conduct these investigations, we have the important tools of a well developed animal model system and two reverse genetic systems with which to manipulate the viral genome.

The following projects are available for rotations

1. Organ specific interferon response to MHV. Investigation of the mechanism by which MHV ns2 inhibits the oligoadenylate synthetase (OAS)-ribonuclease (RNase) L interferon stimulated anti-viral pathway. This includes understanding the importance/role of RNaseL protection from hepatitis. This project involves studies of virus in primary cell types as well as in vivo experiments in mice. This project involves 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 special mechanism by which MHV spreads among neurons, independent of MHV receptor CEACAM 1a in vitro and in vivo during infection of the CNS. This project involves infections in primary neuronal cell cultures and in vivo with JHM and several tropism mutants and variants.

3. Initiation of a T cell response in the central nervous system. The highly neurotropic/neurovirulent JHM fails to induce an effective CD8T cell response in the CNS while other less neurovirulent strains induce a robust response responsible for viral clearance. We believe this is due to a different cellular tropisms and/or interactions with dendritic cells or transport to the cervical lymph nodes. Techniques infections in vivo and in in vitro neuronal cell cultures as well as working with dendritic cells and T cells and flow cytometry.

4. Persistence of MHV in the CNS and demyelinating disease. Following acute infection, MHV RNA genome persists in the CNS and expresses mRNA, in the absence of infectious virus; during this stage of infection, demyelination develops. We are using high throughput RNAseq techniques to investigate the state of the viral genome and the integrity of viral mRNAs during persistent disease. We are in addition elucidating the changes in host transcriptome in the spinal cord of demyelinated mice.



Lab personnel:

Dillon Birdwell- Graduate Student
Ruth Elliott - Research Specialist
Yunbo Jiang- Visiting Faculty
Yize Li- Postdoctoral Researcher
Judy Phillips- Research Associate
Sasha Stone- Undergraduate Student
Joshua Thornbrough- Postdoctoral Researcher
Ashley Wu- Undergraduate Student
Zachary Zalinger- Graduate student
Rong Zhang- Visiting Graduate Student