The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation


"Human immunodeficiency virus type 1 (HIV-1) has evolved a complex strategy to overcome the immune barriers it encounters throughout an organism thanks to its viral infectivity factor (Vif), a key protein for HIV-1 infectivity and in vivo pathogenesis. Vif interacts with and promotes “apolipoprotein B mRNA-editing enzyme-catalytic, polypeptide-like 3G” (A3G) ubiquitination and subsequent degradation by the proteasome, thus eluding A3G restriction activity against HIV-1.
...Our study identifies for the first time a new cellular complex, HDAC6/A3G, involved in the autophagic degradation of Vif, and suggests that HDAC6 represents a new antiviral factor capable of controlling HIV-1 infectiveness by counteracting Vif and its functions. "


http://www.retrovirology.com/content/12/1/53

How the gut microbiome interferes with HIV vaccines.

It seems that HIV looks similar enough to normal, beneficial gut bacteria that we don't produce a strong immune response after vaccination.

take a look @ here:
http://www.independent.co.uk/news/world/ameri...50-per-pill-10511690.html

Absolutely awesome article about computational drug / catalyst discovery:

How big is chemistry? I don’t mean how important is it, or how many people do it, but rather, how many molecules are there that we could make? The answer is, to a first approximation: don’t ask. The number of possible molecular permutations of all the elements doesn’t seem to have been estimated and might not really be a meaningful concept, but even if we limit ourselves to ‘small’ organic molecules (below about 70 atoms) that might exhibit drug activity, the figure is something like 10**60. We haven’t the faintest hope of making any more than a minuscule fraction of them – the largest current public database of molecules so far synthesised, PubChem, contains around 50 orders of magnitude fewer (~70 million). You do the maths.

What we’re looking at here is chemical space, and to all intents and purposes it is as vast as the universe. We’ll never get to explore more than a few little corners. How discouraged should we be? Might there be untold riches here that we’ll never find? Or might we already be rooting around in the most fertile territory?

Drug discovery is the most prominent field for which such questions are pressing, but it’s not alone. Who knows what extraordinary materials might lurk in chemical space – after all, it’s been barely a decade that we’ve been getting to know the potential of one of the simplest materials conceivable, the pure form of crystalline carbon called graphene. Dyes, batteries, catalysts, solvents, food additives, you name it – there’s not a single area of chemistry that might not be enriched by our stumbling into a new region of chemical space. Even if our journeys are doomed forever to remain selective and parochial, can we at least find means of navigation that guide us into the more useful domains? Or are blind, random searches the best we can do?

Many researchers are convinced that it’s not, and they are designing computational and experimental tools to help us do better. While these may bring practical rewards, they also allow us to broach a wider question: can we start to descry the contours of chemical space itself? Do we know what kind of space it is – a uniform plain, say, or a rugged mountainous terrain? And how much of it is actually worth exploring?...

http://www.rsc.org/chemistryworld/2015/09/navigating-chemical-space

When HIV, stripped of the Nef protein, penetrates a cell to infect it, it succeeds without any problem. The virus then replicates normally. But when it comes out again to continue its destructive work in another cell, it takes a part of the infected cell membrane to build its own membrane. With it, it also carries the SERINC5 protein found on the membrane of the attacked cell. From then on, when the virus tries to infect a second cell, SERINC5 acts as an alarm signal and warns the cell that the pathogen is coming. The virus is therefore no longer able to penetrate." Nef, by inhibiting SERINC5, is therefore a crucial element for HIV infectivity.

Usually, Nef is able to neutralize SERINC5. Nevertheless, the study shows that if SERINC5 is highly expressed, Nef is no longer able to counteract it, which greatly reduces the virus infection ability. The goal is therefore to reverse the balance of power to favor SERINC5. "SERINC5 is not the first antiretroviral factor discovered. For sure, we have identified a new element, but, most importantly, we deciphered a mechanism that works very differently from the others. Moreover, contrary to the antiretroviral factors previously discovered, which are activated by interferon (a protein substance produced by certain cells of the immune system in response to a pathogen), SERINC5 is expressed continuously in all cells of our immune system" states Federico Santoni.

http://www.sciencedaily.com/releases/2015/10/151001094719.htm