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Case Study
The origins and
evolution of HIV
Version 1.2
Anne Fischer
Case Stu
Case Stud
Introduction
Prevalence of HIV
HIV (Human Immunodeficiency Virus) is the virus that can lead to AIDS
(Acquired Immune Deficiency Syndrome) in humans. AIDS is a disease
in which the immune system begins to fail, enabling other infections to
threaten the lives of patients. Since 1981, when it first began to spread
widely, HIV has caused the deaths of 25 million people worldwide.
According to current United Nations estimates, HIV will infect 90 million
people in Africa, leaving at least 18 million orphaned children there.
There are several different forms of HIV: evidence suggests that they
originated in Africa, but how are the different forms related to one another
and how did they enter the human population?
A boy sorts maize at the Reitutsire
orphanage in Maseru, Lesotho. The
orphanage is supported by Prince
Harrys charity, Sentebale. Many adults
in Lesotho have been killed by AIDS
leaving a generation of over 380,000
orphans to fend for themselves.
This Case Study uses genetic sequence data from different types of HIV and
compares them with SIVs (simian immunodeficiency viruses), which are
found in wild chimpanzees and gorillas in Africa.
Question
a. Study the map above. Describe the distribution of HIV. Which countries
have the greatest adult prevalence of HIV/AIDS? (Note: the map shows
the incidence of HIV/AIDS, not AIDS-related deaths.)
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Transmission of HIV
HIV, the virus that causes AIDS, can be transmitted through:
unprotected sex (in semen or vaginal fluid);
blood (contact with contaminated material such as needles
and contaminated blood transfusions);
transmission from mother to child during pregnancy or at birth;
breast milk.
The virus was characterised in 1983 by a team from the Institut Pasteur
in France led by Luc Montagnier. In 2008, Montagnier and a colleague,
Franoise Barr-Sinoussi, were awarded the Nobel Prize in Physiology or
Medicine for their discovery of HIV.
An HIV particle (called a virion) is about 100 nm in diameter. This is about
1/20th of the length of a E. coli cell, and about 1/70th of the diameter of the
white blood cells that the virus infects.
A retrovirus
Like all viruses, HIV cannot reproduce by itself. To make new copies of
themselves, viruses must infect the cells of living organisms. HIV can only
replicate within human cells. HIV is a retrovirus. Retroviruses have RNA
(not DNA) as their genetic material. They use an enzyme called reverse
transcriptase to reverse-transcribe their RNA into DNA, which can then
be integrated into the hosts genome and replicated.
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New virus
leaves cell
New virus
assembled
Viral RNA
transcribed
from DNA
Viral protease is
needed to process the
three viral proteins
DNA is transcribed
from viral RNA
Double-stranded
DNA is produced
Viral
integrase
DNA integrates
with the host
chromosome
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HIV denialism
Some people, including scientists who are not experts on HIV, have
suggested that HIV is not the cause of AIDS. They therefore question the
validity of HIV testing and treatment for AIDS. The mainstream scientific
community has rejected these claims. Unfortunately, some governments,
particularly those in South Africa, have until very recently supported
AIDS denialism and encouraged the use of ineffective treatments such as
vitamin supplements. This has contributed to the failure of South Africas
response to its AIDS epidemic, although the situation is improving now.
Question
b. Now you know something about HIV, look once more at the map on
page 2. Suggest several different explanations for the distribution of
HIV/AIDS shown on the map.
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Historical range of the sooty mangabey in West Africa (shown in green). The
geographical range of these monkeys corresponds closely with the occurance of HIV-2
in humans. From: Santiago, M. L. et al. (2005) Journal of Virology 79 (19) 1251512527.
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Chimpanzees and gorillas are the closest living relatives of humans. These
species, as other primate species, are commonly hunted for food (bushmeat)
and orphan chimps are sometimes kept as pets. Such pets are a natural
reservoir for the disease and they could transmit SIVcpz to humans. With
extensive logging of tropical rainforest, access to previously remote areas
is now possible, which further sustains the bushmeat trade.
Chimpanzee.
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Sequence analysis
The aim of this exercise is to study the similarities between SIV and HIV-1
sequences. This will allow you to investigate the potential transmission of
these viruses between great apes and humans.
The data provided are 16 nucleotide sequences from the pol gene of the HIV
and SIV viruses from chimpanzee, gorilla and human. There are six human
sequences, two from each of the three HIV subgroups (M, N and O), two
gorilla sequences and eight chimpanzee sequences. The data file is called:
DNA-HIV1andSIV.geneious
The analysis will be performed using a programme called Geneious. This
software can align sequences and build phylogenetic trees. The nucleotide
sequences will first be translated into protein sequences, which will then
be aligned. From the alignment of the protein sequences, you will build a
phylogenetic tree. This will show which sequences are more closely related
to one another.
1. Double click on the document named DNA-HIV1andSIV.
geneious. This will start the Geneious software and load
the file of genetic sequence data into the programme.
Hint: if a box appears over the Geneious start-up screen, saying that
your trial of the Pro version has ended, click on Use Geneious Basic.
2. The 16 DNA sequences will now open in Geneious:
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Zoom buttons
Questions
c. Use the magnifying glass buttons to zoom in on the sequence data. How
can you tell that it is DNA sequence data and not RNA sequence data?
d. What sort of genetic information does HIV (a retrovirus) have?
e. How has the data therefore been processed before it was given to you?
4. Select all 16 sequences at the same time, by clicking on the file name in
the top window so that it is highlighted:
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Translate button
6. A box will appear, asking you to choose a version of the genetic code to
use. Look at the options available, then choose Standard and click OK.
Note
Although the genetic code is often said
to be universal the same in all
living things this is not quite true.
There are some minor variations in
different groups of organisms. Hence
this dialogue box, which allows you to
choose which version of the code you
wish to use.
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Asp
Glu
Arg
Lys
His
Asn
Gln
Ser
Thr
Tyr
D
Aspartic acid
E
Glutamic acid
R Arginine
K Lysine
H Histidine
N Asparagine
Q Glutamine
S Serine
T Threonine
Y Tyrosine
Ala A Alanine
Gly G Glycine
Val
V Valine
Leu
L Leucine
Ile I Isoleucine
Pro
P Proline
Phe
F Phenylalanine
Met
M Methionine
Trp
W Tryptophan
Cys
C Cysteine
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Tree
button
10. Select the aligned protein sequences (Alignment of 16 sequences) in
the top window, then click on the Tree button to create a phylogeny.
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Technical note
Select JukesCantor and
NeighbourJoining here.
11. A tree will be produced in the lower central window. Re-size the other
windows so that you can study the tree. The software will cluster
similar sequences closer together.
You now have a phylogenetic tree of sequences from the three
subgroups (M, N and O) of the HIV-1 family and their relationship to
SIV sequences from chimpanzees and gorilla.
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Questions
f. Mark, on a paper print out of the tree, using three different colours or
symbols, the branches of the tree that derive from gorilla, chimpanzee
and human viruses.
g. Describe the locations of the HIV sequences in the tree (for example, do
they form any clusters or groups, or are they scattered throughout the
branches of the tree?)
h. Do the HIVs appear to be more closely related to each other, or to some
of the SIV sequences?
i. Do you think that HIV-1 could have originated more than once, and if
so, what was the source on each occasion?
j. Does the geographical distribution of SIV-infected apes overlap with
areas of HIV-1 epidemics? Compare the map on page 2 with the one
below and, if you have access to the internet: www.aidsinafrica.net/
map.php and www.unaids.org/en/
Further reading
Avert, a UK-based AIDS charity, has a website with comprehensive and
authoritative information about HIV/AIDS: www.avert.org
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