Test 1 Study Deck Flashcards
What does AIDS stand for?
Acquired Immune Deficiency Syndrome
What is the average time between contracting HIV and getting AIDS?
10 years
Why is HIV resistant to anti-virals
The replicates as it mutates
What is currently used to treat HIV?
Combination treatment (one pill once a day or an injection every 2 months)
When did HIV emerge?
1920s
When was AIDS discovered?
1981
When was HIV discovered?
1983/84
When was combination therapy introduced?
1995
How many people are currently living with HIV?
35 million
How many people in the U.S. live with HIV?
1 million
What percent of people in the U.S. take HIV drugs?
85%
What percent of people living with HIV are receiving anti-viral treatment?
75%
When was the first HIV patient cured?
2009
Numeracy
the ability to understand and work with numbers
What are the steps of the scientific method?
Observation/question, hypothesis, experiment, analyze data, report conclusions
Pathogenic
able to cause diease
Vector Borne Diseases
disease that results from an infection transmitted to humans and other animals by blood-feeing arthropods (mosquitoes)
Zoonosis
a human gets infected by a pathogen from an animal
Name the 5 stages of animal virus to human virus
- cross-species, spillover
- primary infection
- limited outbreaks
- longer outbreak
- pandemic
epizootic
animal virus that kills a different animal
spillover
the transmission of a pathogen from an animal to a human
When was the first paper about HIV published?
1981
What happened in 1960?
In the DRC, the lymph node was studied, RNA was extracted and doctors were able to line up the HIV genome
TMRCA
Time to the Most Recent Common Ancestor
What is the virus in primates that is very similar to HIV?
SIV
Why did HIV become a pandemic?
social and cultural factors, globalization and mobility, stigmatization and denial, lack of awareness and education
disease triumphalism
an overconfidence in humanity’s ability to conquer diseases
HIV Emergence
Initially a mysterious and poorly understood virus, crossed from primates to humans in central Africa
Lack of effective treatment (1980s-1990s)
no effective antiretroviral drugs available to treat HIV; no medical means to slow down the progression of this disease
high mortality rates
due to cancer and infection
stigma and discrimination
hindered early detection and treatment
vulnerable populations
gay/bi men, intravenous drug users, sex workers, women and people with hemophilia
global spread
first high risk then people of all demographics, the lack of effective prevention and treatment contributed to rapid transmission
public health response
inadequate resources allocated for HIV prevention and treatment, public awareness was limited
community activism
ACT UP
What does ACT UP stand for?
Aids Coalition to Unleash Power
What percent of people living with HIV are women?
60%
GRID
Gay Related Immune Defiency
Describe the stigmatized “gay lifestyle”
too much sex, animal nitrates/poppers, lifestyle mediated
Things that need to happen for virus to be transmissible
physiologic conditions (virus needs to be exposed to someone else in the same conditions because it can’t live outside the body) and a high amount of virus exchanging from infected to the newly infected
undetectable viral load = ?
untransmissible
Where is the virus found?
Blood, semen, breast milk, female vaginal fluid
vertical transmission
mother to child
When were bi/gay men banned from donating blood?
1983/84
When were bi/gay men allowed to donate blood again
late 2022/early 2023
flamaging
10-15 years faster of internal ageing
Triple combo Therapy discovered
1995
FDA approves AZT, the first medication for AIDS
March 19, 1987
the number of reported AIDS cases in the U.S. reaches 100,000
1989
Congress enacts the Ryan White Care Act, providing funding for community-based care/treatment
1990
AIDS becomes the leading cause of death for all Americans ages 25-44
1994
The FDA approves the first protease inhibitor, introducing combination therapy as treatment
1995
Number of AIDS cases in the US declines for the first time
1996
565,000 people have HIV since 1981
2007
The FDA approves use of TRUVADA for pre-exposure
2012
35.3 million people living with HIV
2013
2019
second person with HIV cured
Rock Hudson
One of the first celebrities to die of AIDS, well known actor. Friend of Ronald Reagan.
Vito Russo
Influential activist “Silence = Death”
Howard Temin
Scientist who discovered the enzyme that is critical in HIV lifecycle (UW-Madison) and Nobel Peace Prize
stonewall riots
On June 28, 1969, the Stonewall Inn, a gay bar in New York’s Greenwich Village, was raided by police. But instead of responding with the routine compliance the NYPD expected, patrons and a growing crowd decided to fight back. The five days of rioting that ensued changed forever the face of gay and lesbian life.
GSO
Gay Service Organization
1986 Supreme Court
found sodomy laws were legal, homosexual behavior could be crimminalized, right to privacy did not extend to “homosexual behavior”
ASO
AIDS Service Organization
How did ACT UP draw attention to the AIDS/HIV crisis?
through dramatic and flamboyant actions, made themselves impossible to ignore (chained themselves to fire hydrants, shut down wall street)
“Right to try”
ACT UP won accelerated access to drugs also known as accelerated access trials or “emergency use authorization”
placebo controlled
everyone can respond differently to drugs
GCP
Good community practice, patient representatives/advocacy get a seat at the table because of ACT UP
virus
An obligate intracellular parasite. It needs to invade a living cell in order to copy itself. They cannot make more of itself until they “proactively” infect a cell.
genome
genetic material, can we DNA or RNA, surrounding protein cell/capsid; keeps viral genome safe and helps latch onto cell/wiggle inside
envelope
greasy overcoat, amde form stolen shards of the last cell they infected to spread, a virus has to find a cell
What does the capsid bind with?
outer protein on host cell
polymerase
generates numerous copies of the virus’s genes to produce capsid subunits and other viral proteins
lysing
when new viruses break the shell of the host cell
budding
viruses wrap themselves with a piece of the infected cell and slip through the cells outer membrane; host rarely survives
What cells does HIV infect?
CD4 T Helper Cells
CD4 Receptor
surface receptor that binds to virus
What happens when the virus binds to CD4?
causes a conformational change and allows a second receptor to grab hold of CCR5
CCR5
another surface protein, stands for chemokine coreceptor
How does the virus get into the cell after connecting with CCR5 and CD4?
the virus pierces through the virus into the host cell, drawing the cell and viral membrane together
What happens after the membranes are drawn together?
capsid is disolved, releasing viral enzymes and RNA
What does reverse transcriptase do?
Reverse transcriptase takes the viral RNA and using host nucleotides converts RNA into a single strand of DNA; reverse transcriptase then goes on to create the second strand, the product is double stranded DNA
What does integrase do?
integrase cuts host chromosome and inserts HIV in the host chromosome
What does RNA polymerase do?
Makes mRNA
What does mRNA do?
docks at ER to add proteins; encodes for various viral proteins by associating with ribosomes at the surface of the endoplasmic reticulum (ER); some proteins are produced directly into the ER, others are shuttled
What does the golgi apparatus do?
It shuttles newly created viral proteins and embeds them in the cellular membrane
What does protease do?
Protease breaks up the polypeptide chains into integrase, reverse transcriptase and a new protease
Broad species trophism
disease can infect numerous species
amino acids
give proteins their shape based on interactions and fold
nucleic acids
instructions for making proteins in cells
DNA
blueprint for genome, made of A,T,C,G
What does mRNA convert T to?
U
What is mRNA?
intermediate instruction that encodes amino acid sequences
apoptosis
programmed cell death when creating dysfunctional cells/proteins
necrosis
cell explodes and content are spewed to surrounding area
quiestence
cell is alive but in hibernation
cell signaling
causes the cell to shut down when it detects that something has gone wrong
Of apoptosis and necorsis, which is controlled?
apoptosis
What is the capsid?
It protects viral RNA
What encodes for the capsid?
GAG
why is protease the target of antiretrovirals?
because HIV protease and human protease are different shapes, so the antiretrovirals only attack the HIV
What do DNASe, RNASE and NUCLEASE do?
The degrade DNA and RNA
How many base pairs are in the human genome?
3 billion base pairs
How many base pairs is the HIV genome?
10,000 nucleotides
Why does HIV mutate so frequently?
Because HIV’s reverse transcriptase can not proofread
6 steps of HIV reproduction
- attachment and entry
- reverse transcription
- integration
- gene expression and viral genomic RNA production
- budding
- maturation
lymphatic network
detects any infections that arise in the body
What kinds of cells are usually found in the lymph node?
b cells
b cells
these scan the body for foreign material; each one (there are billions in the body) detects only one kind of foreign infection
The surface of b cells
are covered with receptors that recognize one bacteria/viral protein
triggering activation signal
b cells grab hold of invasive proteins which trigger an activation signal to travel into the cell
what does a b cell do once activiated?
it migrates and begins to replicate; in a few days thousands of copies of the selected cell are made
clonal selection
one cell is selected out of billions of b cells and identical clones of it have been created, therefore, the cell is clonally selected
what do b cells produce
protein antibodies, and then they release them into the surrounding fluid
where do antibodies circulate
the blood and into tissues
how do antibodies trigger immune response
they bond to protein hairs on the foreign bacteria, flagging them for destruction by the immune system; other immune cells inject the antibody covered bacteria to destory and eliminate the infection
what shape are antibodies
y-shaped proteins
where do antibodies attach to viruses
on the outside of the virsus to block them from causing infection; this is called neutralizing
Why do antibodies struggle to stop HIV?
HIV mutates every time it is replicated
bNabs
broadly neutralizing antibodies
vaccines vs. bnabs
vaccines tigger the creation of antibodies whereas when bnabs are injected into the blood, they are present immediately and go stop infection
Ryan White
The Indiana teen got the virus from a blood transfusion as a treatment for hemophilia. He became a household name in 1985 when he fought to be readmitted to public school. His story drew worldwide attention, and he became a spokesman and public face of the disease. He gained attention from megastars like Elton John, who was in White’s hospital room when he died in April 1990. Shortly after, President George H.W. Bush signed the Ryan White CARE Act, which helps more than half of the people in the U.S. diagnosed with the disease.
Freddy Mercury
The flamboyant front man for the band Queen kept quiet about his HIV status until the day before his death from AIDS-related bronchial pneumonia in November 1991. In a final public statement, he wrote: “I felt it correct to keep this information private to date in order to protect the privacy of those around me. However, the time has now come for my friends and fans around the world to know the truth, and I hope that everyone will join with me, my doctors and all those worldwide in the fight against this terrible disease.”
Rock Hudson
Hudson was nominated for an Oscar for his role in the 1956 film Giant, starring alongside Elizabeth Taylor and James Dean. But it was a series of romantic comedies with Doris Day that propelled him to heartthrob status in the late 1950s and early ’60s. He kept his sexuality a closely guarded secret throughout his career and in July 1984 became the first major public figure to announce he had AIDS. He died in October 1985.
Liberace
The famed pianist was known for his over-the top performances, costumes, and piano-top candelabra. Liberace denied claims he was gay, suing both the London tabloid Daily Mirror in 1956 and his chauffeur and secretary, Scott Thorson, who sued for palimony in 1982. When he died in February 1987, his lawyer, manager, and publicist denied he had AIDS. The cause of death was listed as heart failure. But an autopsy showed he had AIDS and died from pneumonia.
Magic Johnson
The basketball legend announced he was HIV-positive in October 1991. The news was a wake-up call to straight men who thought they weren’t at risk for the disease. Johnson retired from the L.A. Lakers but played in the 1992 NBA All-Star Game and helped the U.S. Olympic Team take the gold later that same year. Since then, he’s worked to educate people about HIV and AIDS.
Arthur Ashe
The man who helped break the color barrier in professional tennis revealed he had AIDS in April 1992. He got HIV from a blood transfusion related to heart surgery. Once he went public, he spent the last months of his life raising awareness about HIV/AIDS and spoke about it on the floor of the United Nations. He died of complications from AIDS in February 1993.
Gaétan Dugas
For many years, Gaétan Dugas was presumed patient zero in the U.S., originally termed patient O for “outside Southern California.” He was a flight attendant suspected of picking up HIV in Africa or Haiti and bringing it back to the U.S., transmitting it to dozens of men before his death.
natural history of infection
time from inception to getting cured/death
why was there a higher likelihood of getting HIV from a blood transfusion compared to sex?
In a blood transfusion or use of intravenous drugs, the virus does not have to pass through a physical barrier as it is injected straight into the blood stream
What percent of hemophiliacs have HIV?
90%
What is the rate of infection for heterosexual relationships for the mucosal barrier and for rectal contact?
mucosal -> 1/300
rectal -> 1/30
two requirements for HIV transmission
how many viruses have the opportunity to get across the barrier?
how strong the barrier for the person who is newly exposed is?
zero discordant couples
one has HIV, the other does not
true or false: viral load is not constant throughout the course of infection
true
when are HIV levels the highest?
during the first two weeks of infection because viruses are able to replicate endlessly
Where are the majority of CD4 cells found?
the gut or in GALT
GALT
Gut Associated Lymphode Tissue
Why can HIV infect so quickly in GALT?
HIV can infect cells really quickly because of the concentration of CD4 cells in the gut
How long does the viral life cycle take?
24 hours
How long does it take for an infected cell to get to the gut?
7 days
What percent of cells do HIV destroy after the first 3 weeks of infection?
over 90%
Adaptive immunity
By infecting CD4+ T cells, HIV is able to replicate predominantly in activated T cells and paralyse one of the main components of adaptive immune system.
What are the first two weeks of infection called?
acute or primary infection
What stage comes after acute infection?
chronic infection
Chronic infection
the virus comes down and stabilizes and its set point
Rate of infection for acute infection period?
1/5 chances
elite controllers
low viral setpoint
