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All four of these patients had undergone stem cell transplants for their blood cancer treatment. Their donors also had the same HIV-resistant mutation that dele

All four of these patients had undergone stem cell transplants for their blood cancer treatment. Their donors also had the same HIV-resistant mutation that deletes a protein called CCR5, which HIV normally uses to enter the cell. Only 1% of the total population carries this genetic mutation that makes them resistant to HIV. The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS. A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. [1] Why this treatment still worked is because: However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another co-receptor (CXCR4), but persisted in using CCR5: they either bound to alternative domains of CCR5 or to the receptor at a higher affinity. However, because there is still another co-receptor available, it is probable that lacking the CCR5 gene does not make one immune to the virus; it would simply be more challenging for the individual to contract it. [1] So a mixture of anti-retroviral treatments, which suppress the HIV replication to a point of not showing up in PCR tests anymore (while taking the medication), and (partially?) inhibiting the remaining viruses from infecting cells via the CCR5 pathway, further limiting their replication, caused these patients to be cured. I don't know if the replication slowed down so much that their body was able to kick HIV out once and for all, or blocked it outright because the already reduced number of viruses simply could not beat the odds of infecting via a alternative pathway. Kudos to the researchers! Why is this important: The CRISPR babies[2] had this exact gene removed, and everybody claimed that he cured them from ever getting HIV, even though it's simply not true. Note that there are also drugs which disable CCR5, without gene modification (Selzentry). [1] https://en.wikipedia.org/wiki/CCR5 https://en.wikipedia.org/wiki/CCR5 [2] https://en.wikipedia.org/wiki/He_Jiankui_affair https://en.wikipedia.org/wiki/He_Jiankui_affair

eckesicle 4y ago
It's been a few years now but I used to work on research on this particular alternative receptor. To handwave and simplify a bit CCR5 is the dominant pathway for the virus to spread in a healthy patient. HIV tends to mutate in patients from attaching to CCR5 (called phenotype R5) to CXCR4 (called X4) once the immune system is weaker. Patients with the X4 are not as infectious as a healthy immune system can fend it off. So CCR5 is more or less the only pathway for the virus to infect a healthy host, as far as I can remember.
hn_throwaway_99 4y ago
Your quoted line from the article stated: "Their donors also had the same HIV-resistant mutation that deletes a protein called CCR5, which HIV normally uses to enter the cell. Only 1% of the total population carries this genetic mutation that makes them resistant to HIV." Then you stated: "The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS." I'm not quite sure how you made the leap from "... which HIV normally uses to enter the cell" to thinking the article stated "... CCR5 being the only pathway of the HI Virus to infect your cells", but :shrug:
- biosboiii 4y ago
  Your right, horribly is probably the wrong word, but the same quote said [..] this genetic mutation that makes them resistant to HIV. I don't care so much about the wording in this article, but there have been a lot of efforts for HIV "cures" in the direction of disable CCR5 = disable HIV, which unfortunately is not true. Also when you disable CCR5 on more and more people, the selective pressure may evolve to HIV which primarily targets CXCR4. The way seems to anti-retroviral drugs, and then finish it with CCR5 inhibition.
justinator 4y ago
>The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS. I think the article was just simplifying a very difficult topic in order to reach a mass audience. Very enlightening information that you've added to more illuminate the topic, so chapeau.
- ccooffee 4y ago
  From wiktionary[0]: > chapeau (interjection) - well done, a verbal representation of a hat tip Don't go to wikipedia[1], or else you'll be confused by "A chapeau is a flat-topped hat once worn by senior clerics." Thanks for the new word, justinator! [0] https://en.wiktionary.org/wiki/chapeau https://en.wiktionary.org/wiki/chapeau [1] https://en.wikipedia.org/wiki/Chapeau https://en.wikipedia.org/wiki/Chapeau
  - justinator 4y ago
    de rien

eckesicle 4y ago

It's been a few years now but I used to work on research on this particular alternative receptor. To handwave and simplify a bit CCR5 is the dominant pathway for the virus to spread in a healthy patient. HIV tends to mutate in patients from attaching to CCR5 (called phenotype R5) to CXCR4 (called X4) once the immune system is weaker. Patients with the X4 are not as infectious as a healthy immune system can fend it off. So CCR5 is more or less the only pathway for the virus to infect a healthy host, as far as I can remember.

hn_throwaway_99 4y ago

Your quoted line from the article stated: "Their donors also had the same HIV-resistant mutation that deletes a protein called CCR5, which HIV normally uses to enter the cell. Only 1% of the total population carries this genetic mutation that makes them resistant to HIV." Then you stated: "The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS." I'm not quite sure how you made the leap from "... which HIV normally uses to enter the cell" to thinking the article stated "... CCR5 being the only pathway of the HI Virus to infect your cells", but :shrug:

biosboiii 4y ago
Your right, horribly is probably the wrong word, but the same quote said [..] this genetic mutation that makes them resistant to HIV. I don't care so much about the wording in this article, but there have been a lot of efforts for HIV "cures" in the direction of disable CCR5 = disable HIV, which unfortunately is not true. Also when you disable CCR5 on more and more people, the selective pressure may evolve to HIV which primarily targets CXCR4. The way seems to anti-retroviral drugs, and then finish it with CCR5 inhibition.

justinator 4y ago

>The article is horribly wrong about CCR5 being the only pathway of the HI Virus to infect your cells and ultimately cause AIDS. I think the article was just simplifying a very difficult topic in order to reach a mass audience. Very enlightening information that you've added to more illuminate the topic, so chapeau.

ccooffee 4y ago
From wiktionary[0]: > chapeau (interjection) - well done, a verbal representation of a hat tip Don't go to wikipedia[1], or else you'll be confused by "A chapeau is a flat-topped hat once worn by senior clerics." Thanks for the new word, justinator! [0] https://en.wiktionary.org/wiki/chapeau https://en.wiktionary.org/wiki/chapeau [1] https://en.wikipedia.org/wiki/Chapeau https://en.wikipedia.org/wiki/Chapeau
- justinator 4y ago
  de rien