Lecture Notes

The Lecture Summaries column below gives a synopsis of the topics discussed during each session.

SES # TOPICS LECTURE SUMMARIES
1 Introduction

Overview of class material

Introductions by students and instructors

Instructions about how to read scientific literature (PDF)
2 EBV and lymphoproliferative disorders The first paper shows the discovery of Epstein-Barr virus in a cell line isolated from Burkitt´s malignant lymphoma. At that time the virus was not believed to be of any significance for the actual lymphoma. EBV was later shown to be associated with a number of different human tumors, and the pattern of viral gene expression differs among them. The second paper describes the identification of different EBV transcripts in Hodgkin's lymphoma.
3 MHV-68 as a model in mice for gamma herpes viruses The mouse homologue to EBV is called MHV-68 and has enabled in vivo studies of gamma herpes virus pathogenesis. Establishment of latency and reactivation from latency is a critical aspect of the pathogenesis of herpes virus infection. This paper studies IFN gamma and its control for MHV-68 reactivation from latency.
4 Gastric cancer and Helicobacter pylori I The first paper is the Nobel Prize-winning discovery by Marshall and Warren describing the isolation from and identification of the bacterium H. pylori from the mucosa of patients with ulcers and chronic gastritis. The second paper, published 10 years later, demonstrates the power of being able to genetically modify H. pylori, showing the absence of gastritis in mice upon infection with an H. pylori urease knock-out strain and hence proving that urease is essential for the bacteria to colonize the mouse stomach.
5 Gastric cancer and Helicobacter pylori II

The first paper shows that the bacterial effector protein CagA is sufficient to disrupt mechanisms that maintain normal epithelial differentiation, such as cell adhesion, cell polarity, and the inhibition of migration. The second paper addresses the idea that persistent inflammation fosters cancer development by demonstrating that bone marrow stem cells recruited to the site of microbe-induced inflammation can contribute to metaplasia, dysplasia and cancer. In the first paper the researchers clone a new human papillomavirus (HPV) from the DNA of a cervical carcinoma biopsy and designate it as HPV 18. They show that HPV 18 is found in a large percentage of carcinoma samples, as well as in three cervical cancer-derived cell lines and not in various normal cervical tissue samples.

The second paper describes the role of E6AP, the associated protein of the viral oncogenic E6 protein, in E6-dependent ubiquitination and thus degradation of the transcription factor p53 that acts as a tumor suppressor.
6 Human papillomavirus and cervical cancer I In the first paper the researchers clone a new human papillomavirus (HPV) from the DNA of a cervical carcinoma biopsy and designate it as HPV 18. They show that HPV 18 is found in a large percentage of carcinoma samples, as well as in three cervical cancer-derived cell lines and not in various normal cervical tissue samples. The second paper describes the role of E6AP, the associated protein of the viral oncogenic E6 protein, in E6-dependent ubiquitination and thus degradation of the transcription factor p53 that acts as a tumor suppressor.
7 Human papillomavirus and cervical cancer II The first paper defines an immunogenic epitope for HPV-16 and shows the reaction of the anti-peptide antibodies to a viral nuclear antigen in immunoblotting and immunostaining, which correlates with the diagnostic of cervical intraepithelial neoplasia (CIN) in these samples. The second paper describes one of the original discoveries that recombinantly expressed L1, the major HPV virion protein, can self-assemble into virus-like particles and induce high-titer virus neutralizing rabbit anti-sera capable of preventing HPV infection in vitro. This is one of the papers that forms the basis for the development of the HPV vaccine.
8 Vaccine development process - Guest speakers Researchers from Merck who were involved in the first HPV vaccine efficacy trials will visit our class and talk about the vaccine development process.
9 Hepatitis C, liver cirrhosis and hepatocellular carcinoma The first paper presents the identification of the tetraspanin CD81 as a potential receptor for HCV, by showing binding of the viral envelope protein E2 to CD81. The second paper describes the establishment of a robust cell-culture system for HCV that leads to the production of high levels of infectious particles. The lack of such a system has been a major stumbling block for HCV research in the past.
10 Atherosclerosis as an inflammatory disease I The first paper is one of the earliest suggesting cytomegalovirus as a contributing agent in the process of restenosis (meaning that the treated vessel becomes blocked again, and usually occurs within 6 months after it has been treated with angioplasty) after coronary angioplasty, by describing findings in patients with restenosis lesions. The second paper describes how cytomegalovirus infection of cells may contribute to atherosclerosis.
11 Atherosclerosis as an inflammatory disease II These two papers discuss animal studies that evaluate the effect of cytomegalovirus in the process of atherosclerosis. They show that cytomegalovirus can affect atherosclerosis by different mechanisms.
12 Diabetes and multiple sclerosis as an inflammatory disease The first paper describes the finding of virus-infected (Coxsackie B4 virus) beta cells in the pancreas of diabetic patients. The second paper describes a new view of molecular mimicry as a cause of autoimmune/inflammatory diseases. A molecular mimicry model for multiple sclerosis is suggested based on the T cell response raised by viral/bacterial peptides.
13 Oral presentations During the last lesson each student will give an oral presentation based on his/her written essay. We will also have a discussion about the course and a written course evaluation.