Biology of HIV/AIDS

Fall 2007
TR 10:00 - 11:15, CHM B022
http://www.bio.davidson.edu/people/dawessner/361HIV/index.html

Dr. David Wessner
Watson 218, x2846
Office hours: M 2:00 - 4:00 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 26 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. An estimated 42 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

AIDS: The Biological Basis, 4th ed. 2006. Weeks, B. and E. Alcamo. Jones and Bartlett: New York, NY.
Mountains Beyond Mountains . 2004. Kidder, T. Random House: New York, NY.

Journal Articles

All journal articles are on electronic reserve. To access these articles, go the Library Course Reserves page for this course. Click on 'Connect to Course Reserves.' Enter your network username and password and then browse for this course. Adobe Acrobat Reader is required to view these articles. This software is available on all Library computers and can be downloaded free of charge to your personal computer.

New York Times Articles

Throughout the semester, we will be reading a number of articles from the New York Times that are available on the web. 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.

Assignments

The major assignment for this class is daily participation (60% 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.

Each person also will submit two podcasts (10% each) to The AIDS Pandemic. One must be completed by October 2 and the other must be completed by November 20. Additionally, each person will choose and present to the class a research article during the last two weeks of the semester (15%). Finally, each person will actively participate in a class outreach program (5%) that will culminate on World AIDS Day 2007 (December 1, 2007). I will solicit comments from your peers to determine your level of involvement in this class project.

Schedule

Date	Readings
8/28	Introduction
8/30	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
9/4	HIV Identification 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 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 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 NYTimes - New US report names virus that may cause AIDS NYTimes - A new disease's deadly odyssey
9/6	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
9/11	Guest Speaker - Meg Lafontaine ('04), Centers for Disease Control
9/13	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
9/18	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
9/20	TBA
9/25	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
9/27	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 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
10/2	Role of co-receptors, Pt. II Feng et al. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (1996) 272:872-877 Choe et al. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell (1996) 85:1135-1148 NYTimes - Scientists find elusive protein, HIV's guide
10/4	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
10/9	And The Band Played On, Pt.1 And The Band Played On, Pt. 2 Dinner: 6:30 PM Movie: 7:30 PM
10/11	Guest speaker - Lindsay Cohen Jackson ('99), Litmus, Inc.
10/16	FALL BREAK
10/18	Guest speaker - Lucy Marcil ('06), Peace Corps Volunteer
10/23	Mountains Beyond Mountains
10/25	Mountains Beyond Mountains
10/30	Vaccine Issues NYTimes - FDA authorizes first full testing for HIV vaccine AIDSVAX vaccinations begin in first-ever phase III trial of HIV vaccine. Bus. Wire (1998) Cohen. AIDS vaccine trial produces disappointment and confusion. Science (2003) 299:1290-1291 Cohen. Vaccine results lose significance under scrutiny. Science (2003) 299:1495 Cohen. AIDS vaccine results draw investor lawsuits. Science (2003) 299:1965b Deciphering AIDS Vaccines
11/1	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
11/6	Innate Immunity, Pt. 1 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
11/8	Innate Immunity, Pt. 2 Mariani et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell (2003) 114:21-31
11/13	Guest speaker - Ron Hudson, International Carnival of Pozitivity
11/15	Innate Immunity, Pt. 3 Sheehy et al. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature (2002) 418:646-650 Stremlau et al. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature (2004) 427:848-853 Luban. Cyclophilin A, TRIM5alpha, and resistance to human immunodeficiency virus type 1 infection. J. Virol. (2007) 81:1054-1061
11/20	Microbicides Chang et al. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. PNAS (2003) 100:11672-11677 Rao et al. Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide. PNAS (2005) 102:11993-11998
11/22	THANKSGIVING
11/27	Student Presentations
11/29	Student Presentations
12/4	Student Presentations
12/6	Student Presentations
12/11	Concluding Thoughts