Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

HIV overcomes CRISPR gene-editing attack

nature.com

Post reply on HN
Print view View original

11–20 of 31 posts

Re: HIV overcomes CRISPR gene-editing attack

#11

Post by rpgmaker »

s_q_b wrote: post #5

The biggest problem with HIV is that when you're dealing with one person with "HIV" you're actually fighting dozens of different adaptations of the virus, much like how cancer tumors differentiate into dozens of cell types. My approach would be to compare and contrast SIV and HIV defense strategies in humans and chimps. How does the TRIM5-alpha in chimps manage to fight off HIV, and how does human TRIM5-alpha fight o…

What makes you think that they aren't doing that already? That seems like the first thing anyone would think of doing.

Re: HIV overcomes CRISPR gene-editing attack

#12

Post by adrusi »

nonbel wrote: post #3

I am wondering how they know these mutations were not present to begin with. Also, how many cells were there before the CRISPR treatment vs after? What was the rate at which they divide under these conditions? Perhaps they just killed off enough of the cells with the CRISPR/cas-9 treatment and it took a few days for them to recover to the point of producing detectable CA-p24 (an indicator of HIV) levels.

It doesn't matter if the mutations were there to begin with. Even when the mutation occurs after a change in the environment, it's not the change in the environment that caused the mutation, mutations are random. What matters is if the treatment made the mutations viable.

Re: HIV overcomes CRISPR gene-editing attack

#13

Post by tosseraccount »

nonbel wrote: post #3

I am wondering how they know these mutations were not present to begin with. Also, how many cells were there before the CRISPR treatment vs after? What was the rate at which they divide under these conditions? Perhaps they just killed off enough of the cells with the CRISPR/cas-9 treatment and it took a few days for them to recover to the point of producing detectable CA-p24 (an indicator of HIV) levels.

Original paper is here :

http://www.cell.com/cell-reports/fulltext/S2211-1247%2816%29... CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape

Supplement here : http://www.cell.com/cms/attachment/2052606220/2059839343/mmc...

Known strain to start with. They claim "Both viral targets are very conserved in HIV-1 sequences that are registered in the HIV database (Figure S1B)."

See explanation of figure S1 in supplement for more info.

Re: HIV overcomes CRISPR gene-editing attack

#14

Post by gozur88 »

marshray wrote: post #8
pdkl95 wrote: post #7

Earlier quoted context omitted.

The problem is reverse transcriptase[1] (the enzyme that causes the copy errors) is a key part of how HIV infects the cell[2]. If we could fix that, we could simply block it from working at all, stopping the virus's ability to copy itself into the cell's chromosome. This is actually how a lot of the HIV drugs work (reverse transcriptase inhibitors[3]). [1] https://en.wikipedia.org/wiki/Reverse_transcriptase [2] https…

So then why are retroviruses so relatively rare? Why aren't they the dominant type of virus?

Are retroviruses rare? From what I can tell we don't know much about viruses that don't clearly cause disease.

Re: HIV overcomes CRISPR gene-editing attack

#15

Post by nonbel »

tosseraccount wrote: post #13
nonbel wrote: post #3

I am wondering how they know these mutations were not present to begin with. Also, how many cells were there before the CRISPR treatment vs after? What was the rate at which they divide under these conditions? Perhaps they just killed off enough of the cells with the CRISPR/cas-9 treatment and it took a few days for them to recover to the point of producing detectable CA-p24 (an indicator of HIV) levels.

Original paper is here : http://www.cell.com/cell-reports/fulltext/S2211-1247%2816%29... CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape Supplement here : http://www.cell.com/cms/attachment/2052606220/2059839343/mmc... Known strain to start with. They claim "Both viral targets are very conserved in HIV-1 sequences that are registered in the HIV database (Figure S1B)." See expl…

Ah, I was looking at the other paper so haven't inspected the one you linked to. The two papers used the same method though:

"The HIV-1 LAI stock was produced by transfection of 293T cells with the pLAI molecular clone."

"HIV-1 was first produced by transfecting HEK293T cells with HIV-1 DNA"

Sounds like they produced a bunch of virus in 293T cells, during which time it could mutate.

Re: HIV overcomes CRISPR gene-editing attack

#16

Post by nonbel »

adrusi wrote: post #12
nonbel wrote: post #3

I am wondering how they know these mutations were not present to begin with. Also, how many cells were there before the CRISPR treatment vs after? What was the rate at which they divide under these conditions? Perhaps they just killed off enough of the cells with the CRISPR/cas-9 treatment and it took a few days for them to recover to the point of producing detectable CA-p24 (an indicator of HIV) levels.

It doesn't matter if the mutations were there to begin with. Even when the mutation occurs after a change in the environment, it's not the change in the environment that caused the mutation, mutations are random. What matters is if the treatment made the mutations viable.

Sure it matters. They say that "all mutations cluster around the Cas9 cleavage site at position −3, suggesting that the escape mutations were generated in the process of HIV-1 inhibition." http://www.ncbi.nlm.nih.gov/pubmed/26796669

Perhaps instead the virus that infected some cells that was already mutated, so it was resistant to the cleavage (due to lacking the recognition site).

These are totally different mechanisms.

Re: HIV overcomes CRISPR gene-editing attack

#17

Post by cowsandmilk »

gozur88 wrote: post #14
marshray wrote: post #8

Earlier quoted context omitted.

So then why are retroviruses so relatively rare? Why aren't they the dominant type of virus?

Are retroviruses rare? From what I can tell we don't know much about viruses that don't clearly cause disease.

Wikipedia claims "Over 8% of the human genome is made up of (mostly decayed) endogenous retrovirus sequences"[1]. So, it appears they are at least common enough that we're all passing along endogenous viral elements[2] to our children (and we got them from our parents).

[1] https://en.wikipedia.org/wiki/Noncoding_DNA#Repeat_sequences...

[2] https://en.wikipedia.org/wiki/Endogenous_viral_element

Re: HIV overcomes CRISPR gene-editing attack

#18

Post by mirimir »

Retric wrote: post #6
foota wrote: post #4

Perhaps a stupid question, but the article says "HIV has already shown the ability to evolve resistance to all manner of antiviral drugs (as well as the human immune system). This happens because its genetic material is copied by enzymes that are prone to error. Most mistakes stop the virus working, but occasionally a mutation is beneficial for HIV, allowing it to evade attack." is it possible to fix the gene copying…

The problem is not that it will mutate, the problem is it has mutated so your treatment ends up heavily selecting for that mutation.

Replication with randomness plus selection is just so incredibly powerful.

Re: HIV overcomes CRISPR gene-editing attack

#20

Post by im3w1l »

Let's very pessimistically say this attack killed 50% of viruses, and only those lucky enough to have a mutation at the cleavage site managed to survive, and then multiply after, making the virus immune to that specific cleavage.

Couldn't you then cleave at a few sites at once? With 64 different cleavage sites, only 1/2^64 viruses will survive, meaning it's pretty much completely certain you will kill every last virus.

This assumes none of viruses have some general anti-CRISPR defence, but I think that should be a pretty good assumption.

Post reply on HN