Alcoholism drug can 'wake up' dormant HIV to be killed, study finds

... Sharon Lewin, a University of Melbourne professor who led the work, said that while scientists have made headway‎ into activating latent HIV, one of the main concerns is the toxicity of the drugs trialled. With disulfiram, however, this did not appear to present a problem, she said. "This trial clearly demonstrates that disulfiram is not toxic and is safe to use, and could quite possibly be the game changer we need," she said in a statement. "The dosage of disulfiram we used provided more of a tickle than a kick to the virus, but this could be enough. Even though the drug was only given for three days, we saw a clear increase in (the) virus in (the) plasma, which was very encouraging." ...

http://news.yahoo.com/alcoholism-drug-wake-do...tudy-finds-165621630.html

New amfAR Grants Spur Innovative HIV Cure Research Collaborations

http://www.amfar.org/HIV-Cure-Research-Collaborations/

http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3467.html

RECOMBINASE BREC1 TREND-SETTING FOR FUTURE HIV-THERAPY

Researchers at the Medical Faculty of the Technische Universität Dresden (TUD) and the Heinrich Pette Institute (HPI), Leibniz Institute for Experimental Virology succeeded in developing a designer recombinase (Brec1) that is capable of specifically removing the provirus from infected cells of most primary HIV-1 isolates. The results have now been published in the renowned Journal „Nature Biotechnology“.

With 37 Million HIV-positive people and more than two Million new infections annually, HIV remains a major world health challenge. Even though enormous advances have been made in HIV treatment, a complete cure from the disease is still not possible. Indeed, the propagation of the virus in the body can nowadays be held in check through medication, but the provirus remains present in cells of the body.

A team of researchers from the Department of Medical Systems Biology at the TUD as well as the research unit Antiviral Strategies at the HPI in Hamburg employed directed molecular evolution to generate a designer recombinase (Brec1), which can precisely remove the provirus from the majority (>90%) of clinical HIV-1 isolates found in humans.

The team now demonstrated for the first time, that the approach works on cells directly isolated from HIV-1 patients. Importantly, the antiviral effects were accomplished without measurable cytotoxic or genotoxic side effects. Based on these findings, Brec1 represents a promising candidate for possible applications in improved HIV therapies.

“The generation of molecular scalpels, such as the Brec1 recombinase, will change medical practice. Not only HIV patients will likely benefit from this development, but also many other patients with genetically caused diseases. We are about to witness the beginning of the genome surgery era”, predicts the head of the Dresden group, Prof. Frank Buchholz.

Brec1 recombinase was developed in close collaboration at the department of Medical Systems Biology (Prof. Frank Buchholz), TU Dresden and the Heinrich Pette Institute, Leibniz Institute for Experimental Virology (Prof. Joachim Hauber).

The results were published in the Journal “Nature Biotechnology“:
Janet Karpinski, Ilona Hauber, Jan Chemnitz, Carola Schäfer, Maciej Paszkowski-Rogacz, Deboyoti Chakraborty, Niklas Beschorner, Helga Hofmann-Sieber, Ulrike C. Lange, Adam Grundhoff, Karl Hackmann, Evelin Schrock, Josephine Abi-Ghanem, M. Teresa Pisabarro, Vineeth Surendranath, Axel Schambach, Christoph Lindner, Jan van Lunzen, Joachim Hauber & Frank Buchholz (2016). Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. Nature Biotechnology 2016 Feb 22, advance online publication. doi: 10.1038/nbt.3467.

something new:

http://www.newsy.com/videos/could-a-cure-for-...spReportId=NzgwMzg3MzEzS0

https://www.sciencedaily.com/releases/2016/07/160715112935.htm

How new HIV drugs lock virus in immaturity

A new type of HIV drug currently being tested works in an unusual way, scientists in the Molecular Medicine Partnership Unit, a collaboration between EMBL and Heidelberg University Hospital, have found. They also discovered that when the virus became resistant to early versions of these drugs, it did not do so by blocking or preventing their effects, but rather by circumventing them. The study, published online today in Science, presents the most detailed view yet of part of the immature form of HIV.

HIV, the virus that causes AIDS, comes in two forms: immature and mature. The immature form is assembled inside an infected person's cells. After an immature virus particle has left the cell, it has to change into the mature form before it can infect other human cells. A new group of drugs that inhibit this maturation is currently undergoing clinical trials, but so far it was unclear how exactly these drugs act.

To go from immature to mature, HIV has to cut the connections between its main building blocks, and rearrange those pieces. John Briggs' lab at EMBL and Hans-Georg Kräusslich's lab at Heidelberg University Hospital looked at a particularly important cutting point. It connects building blocks known as the capsid protein and the spacer peptide 1, and if it is not cut, the virus cannot mature. The scientists used a combination of cryo-electron tomography and subtomogram averaging to reveal exactly what this part of the immature form of HIV looks like in 3D. They found that the cutting site is hidden in a position where the virus' cutting machinery can't sever it. So for the virus to mature, the structure first has to change, to expose that cutting point.

"When we looked at the virus with one of these inhibitor drugs on it, we found that the inhibitor doesn't prevent the cutting machinery from getting in, as you might expect," says Florian Schur, who carried out the work in Briggs' lab. "Rather, the drug locks the immature virus structure in place, so that it can't be cut."