HIV/AIDS BIOLOGY
The following packet was prepared by Dr. Burt Jacobs of Arizona State University. We have
included it here to give a more thorough background of the biology of HIV/AIDS. Note that technical
aspects of the biology included here will be more advanced than will be appropriate to teach.
However, it may be very useful in answering complicated questions. Also, please keep in mind that
this information is included online as a supplement to the additional reference material which will be
sent to you with your Participant Handbook.
HIV/AIDS 101
SAFER SEX
A. Abstinence
B. Sexual activity confined to a mutually monogamous relationship, with someone who is not
infected with HIV.
C. Use of a condom (male or female) outside of a mutually monogamous relationship (latex
only, not natural; spermicide (nonoxyl-9) probably not preferable; use only water based
lubricants). Condoms provide a 10-100-fold level of protection compared to unprotected
sexual intercourse.
D. Unprotected sex outside of a mutually monogamous relationship (about a 1% chance of
transmission/act of vaginal intercourse with an infected person). Anal intercourse is more
dangerous (10-100x more dangerous) than vaginal intercourse is more dangerous than
oral sex is more dangerous than mutual masturbation. Receptive partner is more
susceptible than insertive partner (3-10-fold). Presence of a second STD increases the
chance of HIV transmission, 3-10-fold.
Recommended Lubricants
Aqualube
Astroglide
Cornhuskers lotion
Forplay
H-R Jelly
K-Y Jelly
RePair
Probe
Today Personal Lubricant
Unsafe Lubricants
Petroleum jellies
Mineral oil
Vegetable oil
Baby oil
Massage oil
Lard
Cold cream
Hair oils
Shaft
Elbow Grease
Natural Lube
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Sexual Activity According to Degree of Risk for Transmitting HIV
Lowest Risk
Highest risk
1. Abstinence.
2. Masturbating alone.
3. Hugging/ massage/dry kissing.
4. Masturbating with another person but not touching one another.
5. Deep wet kissing.
6. Mutual masturbation with only external touching.
7. Mutual masturbation with internal touching using finger cots or condoms.
8. Frottage (rubbing a person for sexual pleasure).
9. Intercourse between thighs.
10. Mutual masturbation with orgasm on, not in partner.
11. Use of sex toys (dildos) with condoms, or that are not shared by partners
and that have been properly sterilized between uses.
12. Cunnilingus.
13. Fellatio without a condom, but never putting the head of the penis inside
mouth.
14. Fellatio to orgasm with a condom.
15. Fellatio without a condom, putting the head of the penis inside the mouth
and withdrawing prior to ejaculation.
16. Fellatio without a condom with ejaculating in mouth.
17. Vaginal intercourse with a condom correctly used and withdrawing prior to
orgasm.
18. Vaginal intercourse with internal ejaculation with a condom correctly used.
20. Anal intercourse with a condom and withdrawing prior to ejaculation.
21. Brachiovaginal activities (fisting).
22. Brachioproctic activities (anal fisting).
23. Use of sex toys by more than one partner without a condom and that have
not been sterilized between uses.
24. Vaginal intercourse without a condom and withdrawing prior to ejaculation.
25. Vaginal intercourse with spermicidal foam and without a condom and
withdrawing prior to ejaculation.
26. Anal intercourse with internal ejaculation with a condom correctly used.
27. Vaginal intercourse with internal ejaculation without a condom.
28. Anal intercourse with internal ejaculation without a condom.
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LIST OF POSSIBLE SLOGANS PROMOTING
NATIONAL CONDOM WEEK
>>>
>>> Cover your stump before you hump.
>>>
>>> Don't be silly, protect your willy.
>>>
>>> When in doubt, shroud your spout.
>>>
>>> Don't be a loner, cover your boner.
>>>
>>> You can't go wrong, if you shield your dong.
>>>
>>> If your not going to sack it, go home and whack it.
>>>
>>> If you think s/he's spunky, cover your monkey.
>>>
>>> Before you slip between her thighs, condomize.
>>>
>>> It will be sweeter if you wrap your peter.
>>>
>>> Don=t get sick, wrap your dick.
>>>
>>> If you go into heat, package your meat.
>>>
>>> While you=re undressing venus, dress up your penis.
>>>
>>> When you take off her blouse, suit up your mouse.
>>>
>>> Especially in December, gift wrap your member.
>>>
>>> Don't be a fool, vulcanize your tool.
>>>
>>> The right selection, is to protect your erection.
>>>
>>> Wrap it in foil, before checking her oil.
>>>
>>> If you really love her, wear a cover.
>>>
>>> Don't make a mistake, cover your snake.
>>>
>>> Sex is cleaner with a packaged wiener.
>>>
>>> If you can't shield your rocket, leave it in your pocket.
>>>
>>> No glove, No love.
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Cell Biology
The nerve center of the cell is the nucleus (NOTE on sizes: if you were the size of Phoenix, a
single cell in your body would be the size of your bedroom, and the nucleus of that cell would be the
size of your closet. There are about 10,000,000,000,000 cells in your body.). The nucleus contains a
complete set of instructions for making all of the stuff that a cell might need to survive. These
instructions are contained in a blueprint that is 100,000 pages long. The blueprint is a long molecule
of DNA about a billion letters long (if you were the size of Phoenix the DNA in each of your cells
would be a string, the width of a hair, 60 miles long). The color of the blueprint is blue. The
blueprint comes with an index, telling the cell what pages code for which functions. Each cell in our
body actually contains two complete copies of this blueprint, one that we obtained from our mother
and one that we obtained from our father. The two copies are not necessarily identical, and in the
example used below, on page 10 of the blueprint one might code for a ANike track shoe@, while the
other might code for a AReebok track shoe@. The nucleus is surrounded by a membrane (oily cover)
that protects the blueprint from damage.
The actual work of the cell occurs in the cytoplasm, which is the area outside the nucleus.
This region contains all of the machinery to make the cell function. This machinery is made up of
proteins (if you were the size of Phoenix, a protein is the size of a ‘.’ on this page). The instructions
for how to make each necessary protein are found on one page of the DNA blueprint in the nucleus.
Surrounding the cytoplasm is an oily membrane. There are proteins in this membrane that allow the
cell to sense what is going on outside itself (you might think of these as satellite dishes). For
instance, immune cells in your body, which are designed to fight infection, have proteins on their
surface called chemokine receptors. These chemokine receptors bind to proteins released at the site
of an infection. These proteins are
called chemokines. When the
chemokine receptor on the surface
of an immune cell binds to
chemokines released from the site
of infection, the immune cell races
to the site of infection, where it can
help kill the invader. The way that
this happens is that when
chemokines bind to chemokine
receptors on the surface of immune
cells this signals the immune cell to
start making @track shoes@. The cell
looks in its blueprint for the page
that tells it how to make track
shoes. The cell uses a xerox copier
to copy this page 1,000 times, and
sends the copies into the cytoplasm
to the factories that use the copies
of the blueprint to make track
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shoes that the cell uses to race to the site of infection. One important note - When the cell makes
working copies of the blueprint for making track shoes, it makes the blueprint a different color, red
instead of the blue color of the master blueprint, so that it doesn t confuse the copies with the master
blueprint (the master copy of the blueprint is DNA (blue), while the working copies are RNA (red)).
Immunology
When you get infected by a flu virus, the infected cells at the site of infection release
chemicals called chemokines. These chemokines attract cells of the immune system, especially
macrophages and T lymphocytes, which have receptors, called CCR5 and CXCR4, respectively,
for different chemokines. Macrophages indiscriminately chew-up cells in the area, and spit out little
pieces of flu virus onto their surface, thus presenting to the rest of the body what virus is present.
Four different kinds of lymphocytes, B lymphocytes, Thelper lymphocytes, Tkiller lymphocytes and
Tsuppressor lymphocytes, respond to the bits of virus presented by the macrophages.
There are a million different Thelper cells in your body, some of which recognize bits of flu
virus, some of which recognize bits of measles virus, some of which recognize bits of tuberculosis
bacteria, etc. The Thelper cells that recognize flu, bind to the bits of flu on the surface of the
macrophages, thus activating the Thelper cells. The T helper cells start dividing and send-out protein
signals, called lymphokines, that boost-up the response to the virus-infection. One of the things that
this does is make macrophages angry, and thus more efficient at chewing up cells in the site of
infection.
There are two types of specific responses that end-up helping us get over our flu infection.
The first is a Tkiller cells response. There are a million different Tkiller cells in your body, some of
which recognize bits of flu virus, some of which recognize bits of measles virus, some of which
recognize bits of tuberculosis bacteria, etc. The Tkiller cells that recognize flu, bind to the bits of flu
on the surface of the macrophages, and in concert with the signals sent out by the activated Thelper
cells, start dividing and becoming angry. These angry Tkiller cells will recognize flu-infected cells and
kill them. This can kill the cells before the virus has had enough time to force the cell to make new
virus.
The second specific response is by B lymphocytes. There are a million different B
lymphocytes in your body, some of which recognize bits of flu virus, some of which recognize bits of
measles virus, some of which recognize bits of tuberculosis bacteria, etc. The B lymphocytes that
recognize flu, bind to the bits of flu on the surface of the macrophages, and in concert with the
signals sent out by the activated Thelper cells, start dividing and start synthesizing antibodies. These
antibodies are proteins that can, in this case, bind to flu virus and kill it.
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After the macrophages, B lymphocytes and Tkiller cells have done their job, the immune
system must be toned down or else autoimmune diseases will occur. This is the job of Tsuppressor
lymphocytes. There are a million different Tsuppressor cells in your body, some of which recognize
bits of flu virus, some of which recognize bits of
measles virus, some of which recognize bits of
tuberculosis bacteria, etc. The Tsuppressor cells that
recognize flu, bind to the bits of flu on the surface of
the macrophages, and send out signals to tone down
the immune system, and send out signals to kill off
some of the specific B lymphocytes, Tkiller and Thelper lymphocytes that have divided in response to
the bits of flu virus presented on the surface of the macrophages. The Tsuppressor cells never kill off all
of the specific B lymphocytes, Tkiller and Thelper lymphocytes, leaving a memory, such that when you
come in contact with that strain of flu virus again, you can respond quicker, and usually stop the virus
infection before you have any symptoms.
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I. Nature of viruses
A. Associated with disease. Bacteria (prokaryotic cellular), parasites (eukaryotic cellular),
viruses (sub-cellular), chemicals (acellular).
B. Contagious, therefore can reproduce and are "alive".
C. Small (smaller than all known free-living organisms, therefore they must use a cell in
order to reproduce).
D. Obligate intra-cellular parasites.
Viruses are entities that contain a nucleic acid genome (blueprint) of limited capacity and a few
associated proteins (and sometimes lipids). The genome is the blue-print for making new viruses.
The associated proteins 1) protect the viral genome from destruction by ever present nucleases (safe)
and 2) allow the virus to attach to and enter cells (act as an address label) and sometimes 3) provide
enzymes needed for virus replication. Once the virus enters the cell it redirects the cell to produce
new viral genomes, (often using the cell's nucleic acid synthesis machinery), and new viral proteins,
(always using the cell's protein synthesis machinery). New virus particles are assembled from the
replicated components and released from the cells, often killing the cell in the process. For every
virus that infects a cell, over 1,000 new viruses are usually produced.
A virus is composed of a blueprint for making new viruses, a safe to keep the blueprint in, a
mailing label to know where to deliver the virus to, and a few of the tools needed to make new
viruses. NOTE: most of the tools needed to make new viruses are provided by the cell.
II. Human Immunodeficiency Virus (HIV), the causative agent of AIDS (Acquired Immune
Deficiency Syndrome)
A. HIV is a retrovirus
1. Contains an RNA genome (a Ared@ blueprint, 10 pages long, enough to code for
about 10 proteins)
2. RNA is covered with a protein, p7, for protection. Also associated with the RNA
is the enzyme reverse transcriptase, which is a unique, error-prone enzyme
that copies the viral RNA (a “red” blueprint) into DNA (a “blue” blueprint).
3. Surrounding the genome is a protein coat (p24).
4. p7, p24 and reverse transcriptase are made as a long precursor protein that must be
cleaved by a unique viral protease before these proteins can be functional.
5. Surrounding the p24 coat is a lipid bi-layer (derived from the cells plasma
membrane). The presence of this membrane means that the virus can be
inactivated by treating with a mild detergent, such as hand soap.
6. Within the lipid bi-layer are 2 viral proteins, gp120 and gp41. gp120 binds the
virus to cells (binds to the CD4 protein on the surface of cells like Thelper
lymphocytes and macrophages), it is the address label. gp41 induces
fusion between the viral lipid bi-layer and the lipid bi-layer of the cells
plasma membranes. Fusion requires the presence of a chemokine
receptors on the surface of the cell, either CXCR4 (Thelper lymphocytes)
or CCR5 (macrophages). The virus we first get infected with primarily
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infects macrophages, because its gp41 interacts with CCR5 and not with
CXCR4. This changes over the course of the disease, such that the virus that
is around when people progress to AIDS primarily infects Thelper lymphocytes
(these viruses have gp41s that primarily interact with CXCR4). 1% of
Caucasians contain only a mutated versions of the chemokine receptor
(CCR5) on their macrophages, and thus appear to be highly resistant to
infection with HIV. 20% of Caucasians contain one gene for the mutated
version and one normal gene: these individuals take about 3 years longer to
progress to AIDS than individuals with two unmutated copies of the CCR5
gene. Other individuals contain a version of CCR5 that causes rapid
progression to AIDS (these individuals make excess CCR5).
B. HIV replication
1. HIV (present in blood, vaginal secretions and semen, not usually present in
saliva, mucus, breast milk, sweat, feces) binds to cells that contain the CD4
protein (primarily Thelper lymphocytes and macrophages, in blood or in
mucosa). If the cells have the right chemokine receptor the viral lipid bi-layer
fuses with plasma membrane.
2. Viral RNA is copied into DNA (reverse transcribed, this copies the Ared@ blueprint into a Ablue@ blue-print) using the unique viral reverse transcriptase
enzyme (NOTE: uninfected cells in your body do not contain this
enzyme). This process is Aerror-prone@, that is, the viral enzymes make a
mistake such that each viral DNA on average has one mistake in it. Viral
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DNA integrates into the cells DNA and can either remain as a Asilent@
lymphocyte gene, or be actively read to make more HIV RNA blueprint
genome. Note: a silent HIV gene can become actively read in lymphocytes,
when those lymphocytes become activated, such as when they respond to the
particular invader that they recognize, either during an infection or during a
vaccination.
3. The newly synthesized HIV blueprint genome is used to make HIV precursor
proteins. The HIV precursor proteins are cleaved by the viral protease
(NOTE: cells in your body do not contain this kind of a protease) and
used with viral genomes to make new HIV cores that bud out of the cell
picking up a piece of the cells plasma membrane as they leave.
C. Pathogenesis
1. Shortly after infection individuals experience "mono" type symptoms. Virus is present at
high concentrations in the blood at this time (usually about 10 million virus particles
per ml of blood). Within a few weeks to a month, the bodies defenses respond and
knock-down the viral load to about 10-100 thousand virus particles per ml of blood
(antibodies to HIV usually appear within a few
months of infection). At this point the individual
becomes asymptomatic. However, the antibodies to
HIV select for variants of HIV that are no longer
inactivated by these antibodies. Our body then
makes antibodies to these Aescape@ variants, which
selects for new escape variants, etc.
2. The asymptomatic period lasts for an average of
8-10 years. The length of the assymptomatic period
is determined primarily by the virus load in the
blood during the assymptomatic period. During this
time CD4+ Thelper lymphocyte numbers drop from a
normal level of about 800-1000/mm3 to less than
200/mm3. First symptoms are weight loss, night
sweats. Decrease in CD4+ Thelper lymphocyte
numbers leads to severe immune system anergy, and "opportunistic infections and
cancers".
a. Recurrent herpes virus infections (HSV, CMV).
b. Protozoan infections (toxoplasmosis of the brain, cryptosporidiosis of the intestinal
tract).
c. Fungal infections (oral and vaginal candidiasis, pneumocystis carinii pneumonia,
disseminated coccidiomycosis, histoplasmosis).
d. Bacterial infections (mycobacterium avium, tuberculosis, salmonella septicemia)
e. Cancer (Kaposi's sarcoma, Burkitt's lymphoma, brain lymphoma). These are both
caused by viruses, Human Herpesvirus 8 and EBV, respectively.
3. HIV can also infect macrophage-like cells in the brain, often leading to early signs of
dementia.
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4. If left untreated, the average time from diagnosis with AIDS to death is 1-3 years.
D. Treatment
1. Antivirals
a. Reverse transcriptase inhibitors. Nucleoside analogues: Azidothymidine (AZT,
zidovudine), ddI, ddC, 3TC. Non-nucleoside analogues. High toxicity, use
selects for drug resistant HIV.
b. Protease inhibitors. Very effective, with low toxicity. Use selects for drug
resistant HIV.
c. Combination therapy. Very effective. Expensive ($12,000-20,000/year).
2. Anti-fungals. Pentamidine (high toxicity).
3. Immune enhancers.
4. Bone marrow transplants with cells containing an Aanti-viral@ gene.
E. Prevention
1. Education about transmission.
2. Promote condom use and/or monogamy.
3. Vaccine development (many strains, anti-bodies to lab strains do not inactivate fresh field
isolates). AKilled@ virus preparations do not appear highly effective. Live attenuated
vaccines are likely to be risky. Recombinant live viral vaccines using other viruses as
vectors are being tested.
F. Testing
1. Presence of antibodies.
a. ELISA (effective about 6 months after infection)-High sensitivity. High rate of
false positives. Must test positive twice and be confirmed by Western blot
(very low rate of false positives). ELISA method: coat a plastic dish with
HIV. Incubate the dish with patients blood or saliva sample. If the patient is
infected they will likely have antibodies to HIV which will bind to the HIV
on the dish. Incubate with a reagent that turns color if there are antibodies
bound to the dish.
b. Western blot-Very specific for infection with HIV. Very low rate of false positives.
Difficult and relatively expensive to perform. Used only as a confirmation of
a repeatedly positive ELISA test.
2. Presence of virus
a. Antigen capture (Effective from a few weeks after infection to about 3 months after
infection). Fairly insensitive. Method: Coat plastic dish with antibodies to
HIV. Incubate with blood sample. Any HIV in the blood will bind to antiHIV antibodies. Incubate with a reagent that turns color if HIV is present.
b. Viral load test (Effective through-out the course of infection but expensive and
difficult to perform). Two tests, either RT-PCR or branched chain DNA test.
Extremely sensitive, can detect about 50 virus particles per ml of blood.
Method (RT-PCR): take patients blood, copy HIV RNA that is present in the
blood into DNA and specifically amplify the HIV DNA a million-fold.
Detect Incubate with a reagent that turns color if there is HIV DNA present
(can detect as little as 50 copies of HIV RNA/ml of blood). Can be used to
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determine effectiveness of anti-viral drugs and to determine if a new-born is
infected with HIV.
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