Vif antagonists

[dario]

Vif is a protein of HIV.  The chaps at OyagenInc  (see: http://www.oyageninc.com/drugs.htm) are investigating the possibility of targeting this particular protein of the hiv virus that apparently disables an enzyme found in our T Cells with which we attack the bug.  The idea is that by targeting the Vif protein our T Cell enzymes could be free to attack the bug  and  force it to reproduce into new forms that would be  unable to infect new cells.

I wonder if this approach is feasible and what are your opinions ... 

[dario]

This is a better explanation:

The editing enzyme hA3G (also known as CEM15 or APOBEC-3G) serves as our natural defense against HIV-1 infection by inducing C to U mutations in the viral genome as it is being replicated. This results in defective viral proteins and suppression of the infectivity of the HIV-1 virus. The virus can protect itself from hA3G with its own protein called Vif (viral infectivity factor), which interacts with hA3G and tricks our cells into degrading hA3G. As a consequence HIV-1 is able to evade our natural defense. OyaGen has an exclusive license covering its 'lead' compound that functions to inhibit the activity Vif. Our compound antagonizes Vif’s ability to induce the degradation of hA3G thereby allowing the enzyme to catastrophically mutate the HIV-1 genome and reduce infectivity.

[J220]

Interesting. And so it goes....someone will eventually hit the bullseye and defeat this forever. You'll see!

[HIVworker]

There is a lot of work going on to try and exploit APOBEC's destruction of incoming HIV genomes. Vif, as has been said, is the viral defense against this. Target the viral defense and you give the body another advantage.

Truth be said, with all new targets, it depends on where the treatment goes. In all honesty NNRTIs, nukes, integrase, protease, CCR5 antagonists and Fuzeon should do the trick against HIV. However, they don't appear to go where the virus can hide. Future work has also be directed to find the reserve, persistent and latent pools to allow effective eradication. In the absence of this, these new targets represent more tools for people resistant to current therapy. Vif and APOBEC's dance is another piece of this puzzle. I like the idea of targetting other proteins than protease, reverse transcriptase and the envelope as this - at very least - will provide therapeutic options.

R

[dario]

J & R,
thanks for your optimism ... Sometimes I am so down that it is only the optimism of people like you that makes me feel better!

D

[J220]

Just remember Dario, there is actual reason to optimistic. There are so many things happening on the research front, and the wheels of science are turning faster each day, that it's sometimes hard to keep track of everything!

So as I wrote on another post a while back, hope is most certainly merited and warranted, and there is every reason to believe that science will succeed in finding a definitive cure. And yes, there are many who think otherwise, and that is their prerogative, but to them I say this: did anyone forsee that someday there would be a vaccine against cervical cancer?

So I am convinced, from looking at the seemingly exponential advances made in science today regarding hiv, that it's only a matter of time until they hit on the therapy or mechanism that will conclusively work. J.

[eniprac]

Hi guys, I've followed a couple of other threads by HIVWorker, Dario, J220, and a couple of others, and I want to say it's an honour to join your discussion.

This research at DAIDS (http://www.niaid.nih.gov/Daids/vif.htm) seems to indicate that (in the feline model) vaccination with vif-deficient FIV induces nearly complete protection in cats, and increased viral control in monkeys in the SIV model.

While I am not familiar with the mechanisms responsibe for a >99% neutralising response in cats innoculated with vif-deficient FIV upon wild-type challenge, vif indeed appears to be one of the very attractive targets that could give the innate protective mechanisms a reasonable degree of control over HIV in vivo. Most, active of the *active* research that I have been able to find in this direction has focused on passive VIF immunotherapy in the form of VIF antagonists and inhibitors.

I thus have two questions: would inducing vif-specific antibodies be a reasonable approach to control infection, and secondly, what are the possible ways to go about it - delivering pure vif with an adjuvant, recombinant vif, etc...?

Thanks,

Eugene