Bi 1 “The Biology and Biophysics of Viruses”. Lecture 1 Monday March 29, 2010 Organization of the Course. Topic for Bi 1 since 2007: “The Biology and Biophysics of Viruses”. Goal: Introduce biological concepts from a quantitative, molecular, chemical and biophysical perspective.
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Monday March 29, 2010
Organization of the Course
Goal: Introduce biological concepts from a quantitative, molecular, chemical and biophysical perspective.
No memorization (open book problem sets, exams).
Focus on a topic critical to human health: viruses (HIV in particular).
An opportunity to use what you’ve learned to address a real world problem.
Important to ask questions (PJB Office hours Wednesday after class or by appointment).
Recombinant DNA technology, biotechnology
Stem Cell Research
Viral outbreaks (e.g., swine flu)
Why biology needs physics, math, chemistry, computer science, engineering, etc. and why these fields needs biology
Possible careers in fields that use biology
Clinical aspects of AIDS and other viral diseases, social/political issues surrounding HIV/AIDS
Many interesting fields of biology
Office Hours:Tuesdays 2pm; 153 Broad
List of TAs, office hours
Links to relevant websites
Lecture notes, problem sets
Course information, announcements, policies
We will use “clickers” (interactive response pads) to assess success in conveying key concepts.
We will NOT use clickers to take attendance.
Your responses are anonymous -- will not affect your grade.
My major is (or will probably be)
6. Computer Science
I have had taken one or more Biology courses in high school.
1. YES, ≥2 years in high school including AP Biology.
YES, 1 year in high school.
NO, but I took Biology in junior high.
Which is correct?
1. RNA --> DNA --> Protein
2. Protein --> RNA --> DNA
3. DNA --> RNA --> Protein
4. DNA <--> RNA --> Protein
HIV and other viruses are susceptible to antibiotics.
History shaped by epidemics
Bubonic plague in 14th century killed 1/3 of Asian and 1/2 of European population (20 million deaths).
16th century Conquistadors conquered America with measles and small pox.
1700s: European navigators introduce syphilis, tuberculosis and whooping cough to South Pacific Islands. Population of Hawaii reduced by almost 90% by 1860.
Flu epidemic in 1918-19 killed 20-40 million (more than died in WWI).
Christians blamed Jews for bubonic plague outbreaks in 14th century.
15-16th centuries: Italians called syphilis “The French Disease”. French called it “The Italian Disease”.
1930s: Cholera in New York was blamed on the Irish.
Early 20th century: Polio in US said to be caused by Italian immigrants.
A = Acquired = a virus received from someone else
I = Immune = an individual’s natural protection against disease-causing microorganisms
D = Deficiency = a deterioration of the immune system
S = Syndrome = a group of signs and symptoms that together define AIDS as a human disease
* (Centers for Disease Control and Prevention; Atlanta, GA)
HIV infection is not AIDS (is “HIV disease”)
AIDS is umbrella term for 26 known diseases and symptoms
AIDS diagnosis if meet three conditions:
Have one or more of known diseases/symptoms
CD4 T cell count <200/µL
What is CD4? What are T cells?
Test positive for HIVWhat do HIV tests detect?
HIV-1, HIV-2, and SIVsIn nature:HIV-1 and HIV-2 infect humans.HIV-1-related CPZ viruses infect chimps.SIVs infect African monkeys. In laboratories:HIV-1 infects chimpanzees, but does not cause disease. HIV-1 does not infect old world monkeys.Asian macaques infected by some SIV and HIV-2 strains develop AIDS-like disease.
People living with HIV/AIDS: ~33 million
due to AIDS globally, 1990–2007
This bar indicates the range around the estimate
1884-1924 -- (New) estimate for when SIVcpz crossed into humans
1959 -- Earliest known AIDS case: a Bantu man in the Republic of Congo
1981 -- first AIDS cases reported among homosexual males in US
1982 -- AIDS in hemophiliacs, transfusion patients, IV drug users
1983 -- AIDS in US heterosexuals; majority of AIDS in Central Africa affects heterosexuals
1983 -- Virus causing AIDS isolated by groups led by Luc Montagnier (France) and Robert Gallo (US)(SARS virus isolated in 2 weeks in 2003 by international consortium of 13 labs)
1985 -- Blood test to detect HIV
1987 -- AZT licensed for use in AIDS patients
1996 -- anti-HIV drugs (HAART*) reduce AIDS death rates
*Highly Active Anti-Retroviral Therapy
Source: United Nations Population Division (2004). World Population Prospects: The 2004 Revision, database.
Viruses are small* (compared with bacteria) infectious replicating objects that can cause disease in plants, animals, humans. [*5x108 rhinoviruses (common cold) will fit on the head of a pin.]
Viruses are parasites -- they live inside cells of their host animal or plant and reproduce by forcing their host to make new viruses.
Newly-made viruses leave host cell and infect similar cells.
All viruses have a protein coat that encloses genetic material (DNA or RNA). Some also have a membrane (envelope) around the protein coat.
Viruses use host cell machinery to make their components (proteins, carbohydrates, membranes), so they are harder to target with drugs than such as bacteria or fungi (self-sufficient pathogens).
DNA --> RNA --> Protein
Most RNA viruses also follow part of the Central Dogma
RNA --> Protein
Retroviruses: a subset of RNA viruses that reverse usual flow of genetic information within host cell
Reverse transcription of viral RNA into viral DNA
RNA --> DNA --> RNA --> Protein
Three subfamilies of retroviruses
Oncoviruses (cause cancer)
Feline leukemia virus, Rous Sarcoma Virus, Mouse Mammary Tumor Virus
Lentiviruses (slow viruses)
HIV-1 & HIV-2, Feline Immunodeficiency Virus (cats), Visna virus (sheep), caprine arthritis-encephalitis virus (goats), SIV (nonhuman primates)
Spumavirus (not associated with human disease)
(For endogenous retrovirus start here)
~1987 to present: Peter Duesberg (UC Berkeley) believes there is no single causative agent of AIDS, but disease is a collection of non-infectious deficiencies associated with drug use, malnutrition, parasitic infections, other specific risks. (www.duesberg.com)
~2000-2002: South African President Thabo Mbeki made statements that HIV does not cause AIDS, and that AIDS does not exist (>5 million people in South Africa are HIV-positive).
See also Durban declaration (signed by >5000 HIV/AIDS scientists and physicians, released in July 2000) for evidence that HIV causes AIDS:
http://www.thebody.com/atn/346/declaration.htmlA few compelling facts:
Data from matched groups of homosexual males and hemophiliacs shows that only those infected with HIV develop AIDS.
Only HIV-positive mothers transmit HIV to fetuses and only HIV-positive newborns develop AIDS. HIV-negative newborns from HIV-positive mothers do not develop AIDS.
Laboratory and health-care workers with no known risk factors have developed AIDS after exposure to HIV.
Causative agent must be found in all cases of the disease.
It must be isolated from the host and grown in pure culture.
It must reproduce the original disease when introduced into a susceptible host.
It must be found in the experimental host so infected.
“The Human Immunodeficiency Virus (HIV) epidemic has spawned a scientific effort unprecedented in the history of infectious disease research. This effort has merged aspects of clinical research, basic molecular biology, immunology, cell biology, epidemiology, and mathematical modeling in ways that have not been seen before. The ever unfolding discoveries of novel aspects of HIV-host interaction have been accompanied by (and often have resulted from) novel interactions among researchers in the disparate disciplines.”
Coffin, J.M. 1999. Molecular Biology of HIV. In The Evolution of HIV, ed. K.A. Crandall. Baltimore: Johns Hopkins University Press.
Number of HIV cases worldwide at end of 2002
Worldwide, HIV has spread to 70 million people, killed 30 million and is estimated to infect 40 million more in the next decade.
Sub-Saharan Africa has ~67% of world’s HIV/AIDS cases but only 10-11% of world’s population -- home to 87% of 2.3 million children living with HIV/AIDS.
South Africa has highest number of people living with HIV/AIDS in the world (5.5 million in May 2006) and almost one in five South African adults are HIV positive.
National HIV prevalence rate in Swaziland is 33%, the highest in the world.
Fact Sheet: The Global HIV/AIDS epidemic (May 2006)
Kaiser Family Foundation; www.kff.org/hivaids
Opportunistic infections and malignancies in AIDS patients
Rapid weight loss
Recurring fevers, night sweats
Swollen lymph glands
Diarrhea that lasts more than a month
White spots on tongue, in mouth, or throat (thrush)
Red, brown, pink or purplish blotches on skin or inside mouth, nose, or eyelids (Kaposi Sarcoma)
Memory loss, depression, other neurological disorders