Biology of HIV/AIDS

Fall 2010
TR 1:00 - 2:15, Dana 153
http://bio.davidson.edu/people/dawessner/361HIV/index.html

Dr. David Wessner
Watson 218, x2846
Office hours: TR 9:30 - 11:00 and by appointment

In the summer of 1981, an unknown pop singer named Madonna began playing in New York City clubs, a new cable channel devoted to music videos, MTV, went on the air, and the first reports of the disease now known as AIDS appeared in the scientific literature.

In June of 1981, Dr. Michael Gottlieb and colleagues published a short report in Morbidity and Mortality Weekly Report (MMWR) describing a group of patients treated for Pneumocystis carinii pneumonia. As the editors of MMWR noted, P. carinii infections in young, previously healthy individuals were unusual. To add to the mystery, it was noted that all of the patients were homosexual and exhibited signs of a severe immunodeficiency, leading to the speculation that a new, sexually transmitted pathogen could be responsible for this disease. Few people, most likely, speculated that this short report in MMWR was the first documentation of a major epidemic that would affect the world in a horrifically tragic way.

In the 29 years since 1981, researchers have learned a great deal about HIV and AIDS. It is safe to say that we know more about the human immunodeficiency virus than any other virus. As a result of this unprecedented examination of a virus, over 20 drugs effective against HIV have been approved for use in the US. Many people now believe we can view AIDS as a chronic, manageable disease. Yet, we still are faced with a global health crisis. Roughly 40 million people currently are infected with HIV. An additional 15,000 people become infected every day. Seventy per cent of the people with HIV/AIDS live in sub-Saharan Africa. For most of these people, the antiviral drugs are not available; for many, adequate health care is not available. And the ultimate preventative agent, a safe, effective vaccine, remains elusive.

To learn more about HIV/AIDS and the scientific process, we will spend the semester examining the chronology of the AIDS epidemic. By reading the breakthrough articles, and the corresponding news media accounts of these articles, we will trace the history of our understanding of HIV/AIDS. We will focus on understanding the science behind these articles and we will discuss the potential implications of the research. This approach, hopefully, will allow us to gain a better understanding of how we know what we know about HIV/AIDS and also demonstrate how scientific advances are predicated on previous advances.

Readings

Journal Articles

Most journal articles are on electronic reserve. To access these articles, go the Library Course Reserves page for this course. Select the 'Course Reserves' option. Browse for this course and select the appropriate articles.

New York Times Articles

To access these articles, you need to register for the New York Times online (a free service). After registering, you will be able to access these articles.

The Wisdom of Whores (2008). Elizabeth Pisani. Norton & Co. New York.

The AIDS Pandemic

Assignments

Class participation

The major assignment for this class is daily participation (50% of final grade). Quantity and quality of comments are important. As a result, preparedness for class is extremely important. I will assume that everyone has read the material before class and done as much outside reading as is necessary to fully understand the assigned readings. If your background in microbiology, genetics, and molecular biology is weak, you may need to do a substantial amount of background investigation. Coming to class and stating that you didn't understand the material is not an option.

Additional assignments
Essay: What is HIV/AIDS and what should be done?
Length: 2-4 pages
Due: August 31, 2010

Blog and podcast installment: Topic to be determined individually
Length: To be discussed in class
Due: To be discussed in class

World AIDS Day project: Topic to be determined by class
Due: December 1, 2010

Red and Black Ball: To be determined with Warner Hall Eating House
Date: December 4, 2010

Essay: Topic to be announced
Length: 2-4 pages
Due: December 7, 2010

Twitter participation
Ongoing

Schedule

Date	Readings
8/25	Introduction
8/27	Epidemiology of HIV/AIDS Gottlieb et al. Pneumocystis pneumonia - Los Angeles. MMWR (1981) 30:250-252 Gottlieb et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. NEJM (1981) 305:1425-1430 NYTimes - Rare cancer seen in 41 homosexuals NYTimes - 2 fatal diseases focus of inquiry NYTimes - Infant who received transfusion dies of immune deficiency illness Group 1
8/31	HIV Identification? Gallo et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science (1983) 220:865-867. Barre-Sinoussi et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for Acquired Immune Deficiency Syndrome (AIDS). Science (1983) 220:868-871 Group 2
9/2	HIV Identification? Marx. Strong new candidate for AIDS agent. Science (1984) 224:475-477. Everyone Popovic et al. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science (1984) 224:497-500 Group 1 Gallo et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science (1984) 224:500-503 Group 2 Schupbach et al. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science (1984) 224:503-505 Group 3 Sarngadharan et al. Antibodies reactive with human T-lymphotropic retroviruses (HTVL-III) in the serum of patients with AIDS. Science (1984) 224:506-508 Group 4 NYTimes - New US report names virus that may cause AIDS NYTimes - A new disease's deadly odyssey
9/7	National HIV/AIDS Strategy for the United States Group 3
9/9	Role of CD4 Dalgleish et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature (1984) 312:763-767 Klatzmann et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature (1984) 312:767-768 NYTimes - AIDS virus originated around 1930, study says NYTimes - Chimp virus linked to HIV Group 4
9/14	AZT Mitsuya et al. 3'-azido-3'-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III / lymphadenopathy-associated virus in vitro. PNAS (1985) 82:7096-7100 NYTimes - Strong evidence discovered that AZT holds off AIDS NYTimes - Drug found to give patients with AIDS short-term help NYTimes - U.S. to test experimental drug against AIDS on 2,000 victims Group 1
9/16	TBA
9/21	ELISA and Western blot assays Weiss et al. Screening test for HTLV-III (AIDS agent) antibodies. JAMA (1985) 253:221-225 NYTimes - AIDS blood test to be available in 2 to 6 weeks NYTimes - Blood supply called free of AIDS NYTimes - Rock Hudson, screen idol, dies at 59 Hemophilia and AIDS AIDS victim starts school over telephone Indiana judge allows AIDS victim back in school NYTimes - Ryan White dies at 18; His struggle helped pierce myths Group 2
9/23	Guest Speaker Paige Paker: Executive Editor, AIDS.gov
9/28	Role of CD4: Pt. II Maddon et al. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell (1986) 47:333-348 Case of AIDS traced to vaginal intercourse New name is proposed for the cause of AIDS NYTimes - A solitary dissenter disputes cause of AIDS Group 3
9/30	Role of co-receptors, Pt. I Broder et al. The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s). Virology (1993) 193:483-491 Feng et al. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (1996) 272:872-877 NYTimes - AIDS research finds 13 vulnerable spots in virus life cycle NYTimes - An emotional Ashe says that he has AIDS NYTimes - Magic Johnson ends his career, saying he has AIDS infection Group 4
10/5	Long-term nonprogressors - Host Attributes Liu et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell (1996) 86:367-377 NYTimes - Genetic mutation linked to some AIDS protection NYTimes - A new AIDS mystery: prostitutes who have remained immune NYTimes - Scientists see a mysterious similarity in a pair of deadly plagues NYTimes - For unlucky few, gene spurs AIDS stampede Group 1
10/7	And The Band Played On, Pt.1 - In Class And The Band Played On, Pt. 2 Dinner: 6:00 PM Movie: 7:00 PM
10/12	Fall Break
10/14	*Wisdom of Whores*
10/19	*Wisdom of Whores*
10/21	*Wisdom of Whores*
10/26	Fusion Inhibitors Kilby et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat. Med. (1998) 4:1302-1307 Lalezari et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. NEJM (2003) 348:2175-2185 NYTimes - Promise and peril of new drugs for AIDS NYTimes - To combat the wily HIV, newer and safer drugs are necessary The Body - Fuzeon (T-20) approved in the US Group 2
10/28	Innate Immunity - APOBEC3G Goff. Death by deamination: A novel host restriction system for HIV-1. Cell (2003) 114:281-283 Harris et al. DNA deamination mediates innate immunity to retroviral infection. Cell (2003) 113:803-809 Group 3
11/2	A New Strain of HIV Plantier et al. A new human immunodeficiency virus derived from gorillas. Nature Med. (2009) 15:871-872. ScienceNOW - Island monkeys give clues to origins of HIV's ancestor NYTimes - New strain of HIV is discovered Group 4
11/4	Broadly neutralizing antibodies to HIV Burton and Weiss. A boost for HIV vaccine design. Science (2010). 329:770-773. Wu et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science (2010). 329:856-861. Zhou et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science (2010). 329: Group 1
11/9	Guest Speaker - Wes Thompson
11/11	Guest Speaker - Ron Hudson
11/16	Harm reduction strategies The Vienna Declaration Group 2
11/18	The CAPRISA 004 Study Abdool Karim et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide for the prevention of HIV infection in women. Science. (2010) Published online, 19 July 2010. • Cohen. At last, vaginal gel scores victory against HIV. Science (2010) 329:374-375. • NYTimes – African studies give women hope in HIV fight • NYTimes – Advance on AIDS raises questions as well as joy Group 3
11/23	No Class
11/25	THANKSGIVING
11/30	TBA
12/2	TBA
12/7	TBA

Group Members

Group 1
Sarah Little, Pallavi Penumetcha, Jenny Yang

Group 2
Matt Lotz, Rebecca McQuade, Brianna Pearson

Group 3
Caitlin Piper, Scott Connors, Jackie Kim

Group 4
Ashley Crawford, Claudia Carcelen, Sarah Cline