CCR5/CXC4 co receptors

[james3000]

A clinically essential correlate of these findings is that only patients harboring X4 or R5/X4 dual tropic HIV strains should have HIV-infected HSCs. This could be reassuring information, meaning that this theoretically inexpugnable HIV reservoir would only occur late in the course of HIV infection and could be prevented by early initiation of ART.

This doesn't sound very good to me !!!

Does this mean I was infected for a long time ?

[buginme2]

Did you cut and paste that from the middle of some article? Its clear as mud.

If you are asking if someone has cxcr4 tropic HIV have they had HIV for awhile?  Well most people start with ccr5 tropic virus.  Cxcr4 tropic usually occurs later in infection.  I'm sure there are exceptions.  Is that what u were asking?

[james3000]

Sorry I was just looking at CCR5 and the CXCR4 'later in infection' came up.
Seems to suggest to me that  later in infection would = been infected for some years ?
Leads me to believe their is some measure of how long a person may of been infected.
It goes against the know way of knowing factor.

[Inchlingblue]

It's interesting to note that the "Berlin patient" aka Timothy Brown had both CXCR4 and CCR5-tropic virus and yet he was still cured through  stem cell transplants from a donor who had the delta-32 mutation (i.e. someone immune only to CCR5-tropic HIV).

[buginme2]

It's interesting to note that the "Berlin patient" aka Timothy Brown had both CXCR4 and CCR5-tropic virus and yet he was still cured through  stem cell transplants from a donor who had the delta-32 mutation (i.e. someone immune only to CCR5-tropic HIV).

That is interesting, I hadn't heard that before.

From my understanding James. Usually a person is infected with ccr5 tropic virus, after some time (years maybe?) the virus mutates to be dual tropic (cxcr4).  But im sure thts a simplistic understanding of the topic.

[Inchlingblue]

As far as HIV tropism there are three:

Virus that is only CCR5-tropic
Virus that is only CXCR4-tropic
Virus that is dual-tropic, which can use either of the above to attach to a cell.

In early infection it is usually only CCR5. Later it is either both or it is dual-tropic.

[james3000]

So my Cd4 has a CCR5 co receptor and a CXCR4 but my HIV virus is only using the CXCR4 to infect my CD4 t cells because of late stage infection
Would it make sense for some people to start treatment before the virus uses only the CXCR4 ie Maraviroc ?

[buginme2]

What I don't get is, if Timothy Brown was cured because he had new cells that were immune to bein infected with ccr5 tropic virus then why doesnt selzentry (or the other ccr5 tropic drugs in development) also cure?

James not necessarily. I think you can still be initially infected with a cxcr4 tropic virus from thw get go.  It just usually starts as ccr5..........right?

[Hellraiser]

What I don't get is, if Timothy Brown was cured because he had new cells that were immune to bein infected with ccr5 tropic virus then why doesnt selzentry (or the other ccr5 tropic drugs in development) also cure?

James not necessarily. I think you can still be initially infected with a cxcr4 tropic virus from thw get go.  It just usually starts as ccr5..........right?

Timothy may have had all of the dual tropic and X4 cells and reservoirs wiped out during his immune destroying chemo.  No one on HAART will be cured because of reservoirs continually releasing new virus.

[Inchlingblue]

As Hellraiser says basically.

from wikipedia:

Bone marrow ablation is a process whereby the human bone marrow cells are eliminated in preparation for a bone marrow transplant. This is performed using high-intensity chemotherapy and total body irradiation.

Brown went through this process in order to prepare him for the transplant from the donor who's cells lacked the CCR5 co-receptor.

One of the strategies being considered with gene therapy techniques that aim to mimic a transplant such as the one Brown had is for the patient to undergo a milder form of ablation, one that is not as toxic and yet may still do the trick.

[newt]

HSCs stands for hematopoietic stem cells, which make blood cells, including white blood cells like T cells. HSC usually start with both the co-receptors (proteins used by HIV to bind to a cell) CCR5 and CXCR4 but they tend to prefer one or t'other as they mature. There was a long article in the journal Cell (see abstract here: http://www.cell.com/cell-host-microbe/abstract/S1931-3128%2811%2900039-4) which basically showed an analogue for CXCX4 type HIV can infect hematopoietic stem cells in an animal model, the implication being that in humans this may create a reservoir of HIV that's difficult to reach with current treatment.

CXCR4 type virus is associated with a phenomena call syncytia, or large clumps of CD4 cells containing HIV. This tends to be more common in late stage HIV disease (this is different from a long-standing infection). Also, some people have more CXCR4 type HIV from the beginning, and some seem to have none.

People should bear in mind that HIV can get into cells other than T cells, like macrophages etc. Any cell which expresses the CD4 protein can be a target for HIV. CD4 is a protein on the surface of a cell, not a distinct kind of cell in intself.

- matt (nerdy) the newt

Edited for spelling

[james3000]

CXCR4 type virus is associated with a phenomena call syncytia, or large clumps of CD4 cells containing HIV. This tends to be more common in late stage HIV disease (this is different from a long-standing infection). Also, some people have more CXCR4 type HIV from the beginning, and some seem to have none.

What is the difference between late stage and long standing ?
Please explain

Matt (Handsome) Newt

[spacebarsux]

What is the difference between late stage and long standing ?

Late stage HIV infection = very low CD4s and/or recurring OI's aka AIDS defining illnesses.

Long Standing Infection = Being infected for several years.

Long standing Infection DOES NOT ALWAYS = Late stage infection because one could have been infected for several years and still have healthy CD4s and no OI's.

I think....

[newt]

indeed, yes, or alternatively, fall very quickly, as some do

- matt

[newt]

To answer James' question directly (for Mr Spacebar has basically done so) late-stage HIV infection relates to the degree of immune suppression, ie CD4 T cell count of 200 or under perhaps, long-standing means have had it many years. The two do not always match. Some folks can go 10-15 years with little immune damage, some but a year or less.

- matt

[Hellraiser]

To answer James' question directly (for Mr Spacebar has basically done so) late-stage HIV infection relates to the degree of immune suppression, ie CD4 T cell count of 200 or under perhaps, long-standing means have had it many years. The two do not always match. Some folks can go 10-15 years with little immune damage, some but a year or less.

- matt

If your immune system recovers from a "late stage infection" would the CXCR4 cell clusters die out?  Not sure if you know the answer but I'm all kinds of curious.

[Grasshopper]

Are there any concrete correlations between having "syncytium" and disease progression ?

The reason I ask is: I was diagnosed by my primary care physician back in 1992 and then reffer-ed to an ID specialist where elaborate labs were done.
I was then told that my CD'4 were 1300+, no mention of VL, and that I had "syncytium". I then asked what the implications of having syncytium were, and the response was "not completely sure yet, but not very promissing". A year and a half later out of the blue i came down with PCP, which was the beginning of MY nightmare.
Currently I am again at CD4 levels of 1300+  and undetectable.

My next appointment with the ID doc is in the first week of September. I'll ask him about the syncytium thingy.

[Grasshopper]

I found some info, read here :

http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102251005.html
(perhaps 10 years earlier they didn't quite understand the implications)

Dr. van Rij RP  , was the ID doc I mentioned earlier and he worked for the bloodbank Sanquin Amsterdam, and became later the director.

[Tempeboy]

Hi all,

Here is a Youtube clip that I found helpful - http://www.youtube.com/watch?v=oneYI0fhGa0

[Hellraiser]

Hi all,

Here is a Youtube clip that I found helpful - http://www.youtube.com/watch?v=oneYI0fhGa0

Fantastic explanation.

[spacebarsux]

Fantastic explanation.

Agree. Thanks for the link.

[Tempeboy]

HIV also spreads directly between CD4 cells - http://www.youtube.com/watch?v=_iMARhjxXFA&feature=related

It may me that Maraviroc can help prevent this type of transmission, further preserving CD4 cells and reducing viral load.

Research looking at recent 'Thymic Emigrants', or newly formed CD4 cells leaving the thymus gland, found that these CD4 cells did not yet have detectable viral RNA - suggesting the possibility that newly formed CD4 cells in the thymus gland of a person living with HIV are possibly not yet 'positive'.  

This maybe another treatment function for Maraviroc.

Also, Maraviroc has been shown to have anti inflammatory properties, great penetration of the Brain and CSF, great side effect profile, is associated with reduced rates of certain cancers - and recently in Rome was announced to reduce the risk of liver fibrosis in people living with both HIV and HCV.

[james3000]

Thanks that was an Amazing Video