Viruses: Infection and Ecology

Viruses have an enormous influence in our lives.-- daily and historically. The influenza epidemic of 1918 cost far more casualties than World War I, and we still dread the renewed coming of the flu each winter, despite partial potential vaccine protection. The world-wide AIDS epidemic is decimating large parts of Africa and Asia, having an enormous effect on many aspects of life in our world as well, and taxing all that we know about medical care - despite the fact that HIV is a relatively weak virus. The efforts to deal with Foot and Mouth Disease are devastating the livestock industry and economy of Britain and beyond, despite all containment strategies. In a format of lectures, seminar discussions, videos and presentations of student projects, we will explore viral infection in terms of molecular biology, ecology, and physiological and historical consequences. We will begin by looking at well-understood infection processes for a special group of viruses that only infect bacterial cells. These bacteriophages were used to lay the foundations of molecular biology - from the demonstration that DNA is the genetic material to the discovery of messenger RNA to vectors for gene expression. They also play key roles in the natural control of bacterial populations; at any given time, ¼ of the over 10 30 bacteria in the oceans are infected by phages, which make them release their rich nutrients high in the ocean, to be used by other organisms, rather than sinking to be mired in the muck as they die. Insects also have their own viruses, which are important in helping control their natural population cycles. In turn, human impact and climate changes lead to new virus patterns, acute and chronic - Hantavirus, Ebola, influenza, herpes, HIV. We will also explore the components of the immune system and the intercommunications between them and between the immune, hormonal and nervous systems, taking advantage of what we have learned from AIDS and other viral infections and from modern technology. We will explore the apparent roles of viral infections and resulting autoimmune responses in such diseases as juvenile-onset diabetes and chronic fatigue syndrome and consider evidence that viral infection actually has a broad stimulatory effect on certain aspects of the system. Viral infections and the resultant cellular responses also play key roles in certain kinds of cancers and have contributed to our understanding of the basic mechanisms of cancer development from all causes. We will focus here on human papilloma virus and cervical cancer and on hepatitis viruses and cancer of the liver and talk about tumor suppressors, protooncogenes, and the importance of apoptosis, or programmed cell death. Worldwide vaccination against major childhood diseases is a major current goal, with the potential to save lives and suffering, as shown by the eradication of smallpox. However, questions are also being raised about potential negative impacts of vaccination. We will explore questions that should be considered before making any personal or public-policy vaccination decision related to the efficacy of particular available vaccines, the timing and routes of administration, the consequences of the illness and potential long-term implications. This upper-division/graduate program is intended both for those with a strong background in biological sciences and those with a more limited background but a strong interest in the subject.

Because of the range of interests and background levels in molecular biology, I am giving you a choice of 2 Virology books. Those more interested in ecology than in details of molecular mechanisms will probably choose:

Principles of Molecular Virology, Alan Cann 3rd ed. [with CD]

For those with a strong molecular background and interest, I recommend the excellent new:

Principles of Virology: Molecular Biology, Pathogenesis and Control of Animal Viruses. Flint et al. 2nd Ed.
-> Searchable index here -> (pdf)

(This has substantial advantages over the first edition.)One major focus will be immunology as related to virus-infected cells and the pathogenic consequences. Major strides of the last few years are beginning to bring some order to this terribly complex field, and this is reflected in:

Immunobiology, Janeway. 6th ed

which I have also orderedfor this class. We will focus on those parts most relevant for viral infection, but it will also be an excellent future reference.

Bacteriophages: Biology and Applications. Kutter and Sulakvelidze (2005)
-> Relevant Chapters Here <-

General principles:

• This is an upper division/graduate course, and I expect you to work with a substantial amount of initiative and independence, producing work appropriate to your background and direction.
• Expect to put in a total of 3 hours/week/credit – i. e., an additional 8 ½ productive working hours in addition to the 3 ½ hours in class. Part of this will be general assignments, part more related to topics of your own particular interest.
• Be in class and be punctual. If people are on time initially and after breaks, we will generally be out by 9:30. If it is impossible for you to be here in a given week, leave an email (or phone) message to that effect in advance and then arrange how to make up your work, including notes from others.
• Evaluations will be based on class participation, 3 integration papers, a detailed portfolio of your work throughout the quarter, and a final research project (prepared and presented in small groups) and a few assignments to turn in.

Syllabus - Viruses -

This will be finalized in conjunction with the class, reflecting their particular needs and interests, and will include both student and faculty presentations.

Week

Topics and Activities

Readings

Week 1

Introductions: brief statement of backgrounds and particular focus.

Bacteriophages as models: basic phage biology chapter linked to program web page

Definitions, general classification, ecological and evolutionary overview

http://www.tulane.edu/~dmsander/WWW/224/Classification224.html,

http://www.virology .net/Big_Virology

(Cann, Ch. 1 and 2 – pg. 1-53 or Flint, pg. 1-61)

Week 2

Writing and small-group discussion: what do you know; what do you want most to learn?

Defining the questions -- your choice of a book about influenza epidemics, AIDS, or another emerging viral pathogen, used particularly to define some of the questions and problems and put viruses in a social context. (I encourage you to start this reading in advance, but I will have some books available that can be borrowed if you need one.) You will first hold discussions in smaller groups related to your particular virus, then present and discuss further with the whole class. Some suggestions:

1. Influenza (1918 pandemic to current Bird Flu concerns): John Barry; Pete Davies; Gina Kolata

2. HIV/AIDS; examples:

3. Extremely lethal, fast-acting viruses, such as Ebola, Lassa, Hanta: Virus Hunters of the CDC; Coming Plague

Coming Plague 281-390; Virus Hunters of the CDC 9-25 and 162-195; Randy Shilts (Band Played On) – and a number of others. [also recommended: first reading of Flint ch. 17 – 623-651, HIV pathogenesis, or HIV pieces in Cann]

Week 3

First integration paper due, setting your own stage after weeks 1 and 2.

Discussion of potential research topics and interests – begin to set up teams for projects, which will be presented in weeks 9 and 10.

Introduction to Immunology and viruses:

Macrophages, dendritic cells, epitope presentation and superantigens; T-cell responses

Snacks: Felix, Jessica D, Savahn

Janeway, 1-43, 69-85

Flint Ch. 15

Week 4

Large DNA Viruses: Herpes and Adenovirus
--> Herpes Packet for printing <-- (2.5Mb)

**Skim assigned book readings with particular attention paid to Herpes, Flu, Adeno, and Filoviridae.

Molecular Mechanisms of Phage Infection <-- (~13.9Mb) and other chapters from...

(Bacteriophages: Biology and Applications. CRC Press 2004, Ed. Kutter & Sulakvelidze)

Snacks: Diana, Heather, Josh

Flint 65-80; 109-124; 182-212; 253-324. Genomes Replication and Transcription. Cann 56-156.

Week 5

Shapes recognition and the course of the adaptive immune response to infection.

Snacks: Seamus, Jessica L, Teresa U.

Janeway 102-131; 665-681 (evolution) focus on shapes and recognition. Also of course the adaptive immune response to infection: Ch. 10 -esp. viral, T-cell

Week 6

T cell gene development and function; Vaccines

Immunology Workshop 2 <-- (20kb)

2nd Integration paper due

Snacks: Issac, Mike, Sonia

Janeway 319-361; Vaccines 642-657; Flint 703-725; Ch. 19; Cann see: Vaccine refs.

Week 7

Snacks: ?, Carly, Dealla

Week 8

Guest Speaker:

Heather Zwickey, Director of Research, Assistant Professor (immunology, research and statistics); Ph.D., from National College of Naturopathic Medicine, Portland, will be speaking about virsues and the immune system

Snacks: Kari, Brian, Trevor

Flint 540-545, 550-556

Week 9

Abstract
-annotated bibliography
-key papers

1 original article
-critique
-does it prove?
-questions it leaves
-well written

Copy of ppt.
-relevant readings for class

Jason, Savahn
Josh, Felix
Kari, Heather, Diana
Seth, Mike
Seamus

Snacks: Andrea, Emily, Chris

Presentations:

EIV

HPV_Carly

H5N1

HCV

NanoTech

HPV_Teresa_Dealla

TBV Sara, Isaac

Week 10

Dealla, Jessica L, Jessica D, Teresa
Emily, Andrea
Adam, Chris, Trevor
Brian
Issac, Sarah

Snacks: Sara, Jason