Evolution Lecture 2: HIV
HIV Evolution and Natural
• Transcription errors produce mutations in the
reverse transcriptase gene. Virions carrying
mutant reverse transcriptase gene produce
versions of the reverse transcriptase enzyme that
vary in their resistance to AZT
• The mutant virions pass their reverse transcriptase
genes, and thus their AZT resistance or
susceptibility, to their offspring. In other words,
AZT resistance is heritable.
• During treatment with AZT, some virions are
better able to survive and reproduce than others
• The virions that persist in the presence of AZT are
the ones with mutations in their reverse
• AZT resistant populations do not reproduce
efficiently when AZT treatment is halted
• Back-mutations restore AZT resistant rev.
trans. To the normal rev. trans. When AZT
is not present. The original configuration is
then favored by natural selection.
Evolution and Further
• Since HIV evolves so quickly, what we need is to
increase the number of mutations a virion needs to
survive. We would like to do this so that the
number of mutations required becomes prohibitive
• Add new pressures…a cocktail of drugs:
– Rev. trans. inhib
– Protease inhib.
– Fusion inhib
– Integrase inhib
Selection Pressure from Killer T-
• Killer T-4 cells Recognize epitopes (viral proteins
displayed on the surface of the infected cell).
• HIV evades detection by changing epitopes
• HIV produces 10-100 million virions a day, with
an abundance of mutation and changed epitopes.
• Over 10 years, virion’s gp 120 gene diverged by
8%(2% difference in human and chimp…not a fair
Why does divergence asymptote?
Collapse, therefore no
selection to make novel
• CCR5 and CXCR4 are two types of co-receptors
found on T4 cells. CCR5 replicates quickly and
thus are infected first.
• As infection increases, HIV will switch to CXCR4
(b/c they begin to divide more rapidly to take over
for the decreasing CCR5).
• This ultimately hastens the death of the host. Why
would this happen?
Natural Selection and Evolution
are Not Goal Oriented.
• HIV population in a single host evolves itself out
of existence by killing that host…unless it spreads.
• Those that attack both CCR5 and CXCR4 are
probably good at replication and infection.
• This helps them overcome another level of
selection…strains that reproduce more are found
in higher quantities in bodily fluids and are thus
able to become transmitted to other hosts more
• Therefore their lineage does not die
Benign Forms of Aids and Low
• Sydney Bloodbank case and the special strain of
aids that only infects CXCR4. Not as deadly b/c it
does not reproduce efficiently
• Lack of portion of Nef protein does not allow the
virus to gain entry into cell, boost viral replication,
and thus less immune response from host.
• HIV-2 poor transmission among hosts and not as
• Why are these strains so rare in nature? Inability
to reproduce efficiently limits the concentration of
virions in hosts blood, thus poor transmission.
Review of the two levels of
selection in nature against aids
• Variation in levels of ability for virus to
survive and reproduce in host
• Variation in ability to become transmitted
from host to host.
• These two types of selection are obviously
tied. Think of an example where being
good at the first limits being good at the
Selection Against Host and
• Some humans have unusual coreceptors on
the surfaces of their cells.
• Deletion of 32 bp in CCR gene, bars virion
• In parts of Europe >14% of population has
this gene. Why?
• Natural selection?
• Drift?…small populations…Vikings?????
HIV Origin and Reconstruction
of Evolutionary History
• Phylogeny…diagrams evolutionary
• How to read a tree:
– Node..branching point for common ancestors
– Branches (internodes)…line of evolution leading to
– Branch length may indicate genetic distance or time (in
– Monophyly, paraphyly, and polyphyly
1. HIV-1 and HIV-2 Not related
2. HIV-2 in humans related to Sooty
4. SIVcpz was transmitted to humans by chimps
Transmitted from chimps 3 times
When Did HIV Move from
Chimps to Humans
Legal Cases Involving Aids
• 1998-Lafayette, LA, Woman claimed
physician injected her with HIV infected
• In Florida a woman claimed to have
obtained HIV from dentist.