Download HIV Coloring

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HOW HIV INFECTS CELLS
In general, viruses have very small genomes which means that they don’t have many genes. Also, their genetic
information encodes few of the proteins needed for reproduction. For this reason, most viruses must use the
proteins provided by their host in order to reproduce (make more viruses). In a way, viruses are parasitic; they bring
very little with them and steal what they need from the host cell. Because they cannot reproduce on their own,
viruses are not considered living organisms; they are simply genetic information, either DNA or RNA packaged within
a protein and/or membrane coat.
AIDS (Acquired Immuno-Deficiency Syndrome) is one of the worst pandemics the world has ever known. HIV
(Human Immunodeficiency Virus), the virus that causes AIDS, was first discovered in 1981 in a remote area of
central Africa. It has since swept across the globe, infecting millions in a relatively short period of time. AIDS has
killed more than 28 million people that we know of, with up to 3.6 million people dying in 2005 alone. While many
cases go unreported, the prevalence of the disease is increasing. By comparison:
 The flu pandemic of 1918 killed approximately 20 million people worldwide.
 World War II killed approximately 40 million people.
Clearly the AIDS pandemic has had, and will continue to have, a significant and global impact.
The Structure of HIV
The HIV (human immunodeficiency virus) has a lipid membrane similar to the cell membranes of other organisms
made of phospholipid and proteins. Color the HIV lipid membrane (d) light green. Within the membrane are several
attachment proteins (a) which are used to attach to the host cell. Color the GP120 attachment proteins (a) brown.
Within the membrane is another layer of proteins that comprise the capsule (b) which surrounds the viral core.
Color the capsule light blue. The most important part of the virus is its genome, which is two separate strands of
RNA. Color the viral RNA genome (c) pink. On the picture, there are several instances of the viral RNA, make sure
they are all colored pink. Also important to the virus are the enzymes that will convert the RNA to DNA - reverse
transcriptase, an enzyme that is unique to RNA viruses. Color the reverse transcriptase (e) yellow. Because the HIV
virus uses the reverse transcriptase and has an RNA genome, it is known as a retrovirus. Because HIV has single
stranded genetic material which depends on reverse transcriptase, it develops mutations more frequently than DNA
viruses because reverse transcriptase has a high error rate. The changing nature of a retrovirus results in
difficulties when developing vaccines against them. Virus exhibit various mutagenic rates: 1) HIV mutates so quickly
vaccines have not been able to be produced, 2) Influenza requires a new vaccine every year due to changes in the
virus, 3) Polio requires one vaccine in a lifetime.
Drugs such as AZT work by inhibiting the function of reverse transcriptase, thus preventing the virus from
converting the RNA to DNA.
HIV Infection
HIV infects a particular type of immune system cell, the CD4 + T-Helper cell, or just plainly, the T-Helper cell. Once
infected, the T-Helper cell turns into an HIV replicating cell. HIV will slowly reduce the number of these cells until
the person develops the disease AIDS with death usually due to an opportunistic infection. T-helper cells recognize
antigens engulfed by a phagocytic macrophage and once bound to the complex releases lymphokines that stimulate
other helper T cells and help activate cytotoxic (killer) T cells and B cells. Killer T cells kill virus infected cells, body
cells that are cancerous, and are involved in tissue rejection. B cells are lymphocytes that reside in lymph nodes and
spleen are induced to replicate by antigen bind and Helper T cells and either produce some antibodies, plasma cells
which are antibody producing machines, or memory cells.
Step 1 - HIV enters the host cell after attaching to specific host receptors (antigens) called CD4 cell surface
antigens. It is as if the virus has a specific key that only works on the host cell with the right lock. In the case of
HIV, the lock is the CD4 cell-surface antigen located on the surface of T Helper cells. Colar the CD4 antigens
(labeled q) dark green. CD4 antigens are located on the cell membranes (labeled f) of the cell colored black.
Step 2 - At this point, the virus and the cell membrane fuse and the virion core enters the cell. The core contains
the viral RNA genes and viral proteins. The viral RNA and core proteins are released into the cytoplasm where
reverse transcriptase converts the viral RNA to viral DNA. The viral RNA is colored as above, and the viral DNA (h)
should be colored red.
Step 3 - Viral DNA, a complementary DNA then double stranded DNA is transported into the nucleus1 (continue to
color all instances of viral DNA red) through the nuclear membrane (n) pores. Color the nuclear membrane (n) grey.
In the nucleus, the enzyme called integrase fuses HIV viral DNA with the host cell's normal DNA. Viral DNA can
persist within the cell's DNA for many years in a latent state, which further complicates efforts to treat or cure
the disease. Lightly color the host cell DNA blue in all instances (labeled g). Using the host’s cellular enzyme RNA
polymerase, the viral DNA is transcribed into two splices of RNA, a shorter splice (j) and a longer splice (i) which are
destined for two different things. Color the short splices (j) pale yellow and the long splices (i) orange in all
instances.
Step 4 - The short spliced RNAs are transported to the cytoplasm and ribosomes where their message is used to
create viral proteins which will become part of the completed virus. Color the golgi apparatus (k) purple and the
processed viral proteins (m) as you did in the other instances (attachment proteins brown). The longer splices are
the full length viral RNA and will become the core of new viruses. Another enzyme, called protease is needed to
assemble the proteins into their final functional forms. Protease inhibitors are another drug used to combat AIDS.
Step 5 - Using the proteins assembled from the golgi apparatus and the completed viral RNA from the long strands,
the mature virus buds off from its host cell. The process of budding destroys the host cell.
a) attachment proteins - brown
b) virus protein capsule – light blue
c) viral RNA - pink
d) viral lipid membrane - light green
e) reverse transcriptase - yellow
f) host cell membrane - black
g) host DNA - blue
h) viral DNA - red
i) long splice viral RNA – pale yellow
j) short splice viral RNA - orange
k) golgi apparatus - purple
m) incomplete viral proteins - brown
n) nuclear membrane - grey
q) CD4 antigens - dark green
Questions
1. Explain the role of each of the following in HIV infection
--protease
--reverse transcriptase
--CD4 receptors
-- RNA polymerase
--integrase
2. What is a retrovirus?
3. What do the long splices and short splices of RNA become?
4. There are two drugs that can reduce the spread of HIV infection in cells described herein. List these
two and how they work to stop the spread. Design – think of a drug that might also slow the rate of
cellular infection. Describe how the drug will work either on the virus or the host cell.
1
http://www.ncbi.nlm.nih.gov/pubmed/16409631 - how double stranded HIV DNA enters the cell is an area of active research.
Legend
g