Chapter 1 UCF Evolutionary Biology (PCB4683)

How is HIV transmitted?

Sexual contact

Needle Sharing

Blood Transfusions

Breastfeeding

Childbirth

Where are the majority of new HIV infections found?

Low to middle-income countries

What percentage of children make up new infections?

7%

What country has the largest number of people living with HIV and the biggest declines in new infections ?

Africa

What is HIV?

obligate intracellular parasite

Which cells are vulnerable to HIV?

Dendritic cells

Effector helper T cells

Memory helper T cells

(all carry CD4 & CCR5)

How does HIV initiate replication?

by binding to two proteins on the surface of a host cell.

first to CD4, found on the surface of certain macrophages and T cells

second to a coreceptor, which fuses the envelope around the virion with the host cell membrane and spills the contents of the virion into the cell.

What contents of the virion are spilled into the cell?

viruses diploid genome and three proteins:

reverse transcriptase

integrase

protease

Reverse Transcriptase

transcribes the virus's RNA genome into DNA

Integrase

splices the DNA genome into the host cell's genome

Protease

plays a role in the preparation of new viral proteins

Complex life cycle of HIV

Made possible by reverse transcriptase

Uses host cell's own machinery to reproduce

Preventing the manufacture of virions often stops the host cell's normal processes

How does HIV cause AIDS?

Destroys virions in the bloodstream

Kills its own infected T cells & macrophages

How long after an HIV infection, without treatment, will a human develop AIDS?

approximately 10 years

Death occurs how long after AIDS develops without treatment?

approximately 2 years

How did AZT (azidothymidine) seem to be a promising drug?

it interferes with reverse transcriptase

stops transcription of DNA

Where does AZT (azidothymidine) insert itself?

in thymidine's place in the growing DNA strand

Why does AZT work in the short run and fail in the long run?

After 2 years of use, CD4 T- cell levels of patients begins to drop again

Transcription errors lead to mutations in reverse transcriptase gene

Mutations produce variability in enzyme function

Some virions survive better than others in the presence of AZT

These advantageous mutations are passed on to the offspring of AZT-resistant virions

reverse transcriptase is...

prone to mistakes

mutations arise very frequently

Why did AZT stop working?

overtime the individual viruses with mistake prone reverse transcriptase start to die out

Natural selection is not

unidirectional or irreversible

Coreceptor inhibitors

block HIV from attaching to cells

Entry/Fusion inhibitors

bar entry to host cells

Non-nucleotide RT inhibitors

block reverse transcriptase allosterically

Integrase inhibitors

block viral DNA incorporation into host DNA

Protease inhibitors

block the enzyme that cleaves precursor proteins to allow maturation of virions

What is HAART?

Highly Active Anti-Retroviral Therapy = more than two drugs

It's much harder for resistance to evolve to multiple drugs at once. Therefore, it lengthens lifespans

Where did HIV come from?

it was derived from one of the SIVs and that the global AIDS epidemic started when this SIV moved from its primate host into humans.

What is a phylogenetic tree?

it shows the historical relationships among a group of viruses or organisms.

HIV-1 likely came from

chimpanzees (East Africa)

HIV-2 likely came from

sooty mangabeys (West Africa)

What are the four groups of HIV-1?

group M- Major/Main

group N- Non-M, Non-O/New

group O- Outlier

group P- Pending

Group M- Major/Main

has differentiated into 9 subtypes

from chimps, Global (95% cases)

Group N- Non-M, Non-O/New

<20 infections recorded (2015)

from chimps, Cameroon only

Group O- Outlier

High-diversity, West-Central Africa

from chimps?

Group P- Pending

one case (Cameroon)

from gorillas? both via chimps?

or humans to gorillas?

Why is HIV fatal?

"selection thinking"

it doesn't slow down its reproduction rate so that it doesn't kill its host and can transmit to more people over a longer period of time

Virulence is caused by

reproduction rate of virus

What does HIV have to do before its host dies?

colonize a new host

high replication rate =

more transmissions/year, but also fewer years to spread

selection favors...

intermediate virulence

HIV-2 and the Non-M HIV-1s

are milder but spread slower

Transmission Rate Hypothesis (1)

natural selection favors high rates of virulence for STIs when partner exchange is frequent, low rates of virulence when partner exchange is infrequent.

Second Hypothesis

Virulence results from trade-off between natural selection working at two levels: within hosts and between hosts.

Third Hypothesis

When SIV first moved to humans, it was still adapted to the immune systems of non-ape primates, where it is benign. This mis-match made HIV more virulent than optimal for transmission.