Navigation Links
HIV researchers solve key puzzle after 20 years of trying
Date:1/31/2010

Researchers have made a breakthrough in HIV research that had eluded scientists for over 20 years, potentially leading to better treatments for HIV, in a study published today in the journal Nature.

The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.

Prior to the new study, which was funded by the Medical Research Council and the US National Institutes of Health, many researchers had tried and failed to work out the three-dimensional structure of integrase bound to viral DNA. New antiretroviral drugs for HIV work by blocking integrase, but scientists did not understand exactly how these drugs were working or how to improve them.

Researchers can only determine the structure of this kind of molecular machinery by obtaining high quality crystals. For the new study, researchers grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.

Over the course of four years, the researchers carried out over 40,000 trials, out of which they were able to grow just seven kinds of crystals. Only one of these was of sufficient quality to allow determination of the three-dimensional structure.

Dr Peter Cherepanov, the lead author of the study from the Department of Medicine at Imperial College London, said: "It is a truly amazing story. When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago. Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallization. Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded."

After growing the crystals in the lab, the researchers used the giant synchrotron machine at the Diamond Light Source in South Oxfordshire to collect X-ray diffraction data from these crystals, which enabled them to determine the long-sought structure. The researchers then soaked the crystals in solutions of the integrase inhibiting drugs Raltegravir (also known as Isentress) and Elvitegravir and observed for the first time how these antiretroviral drugs bind to and inactivate integrase.

The new study shows that retroviral integrase has quite a different structure to that which had been predicted based on earlier research. Availability of the integrase structure means that researchers can begin to fully understand how existing drugs that inhibit integrase are working, how they might be improved, and how to stop HIV developing resistance to them.


'/>"/>

Contact: Laura Gallagher
l.gallagher@imperial.ac.uk
44-020-759-48432
Imperial College London
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/8/2016)... ... December 08, 2016 , ... The West Virginia ... 1, 2017. The name change aligns the entire company with its existing ... care quality. , “We are very proud of the achievements associated with the ...
(Date:12/8/2016)... ... December 08, 2016 , ... After enjoying record-breaking attendance at ... for its 33rd Annual Issues & Research Conference, March 2-3, 2017, at ... the conference is “Persistent Challenges and New Opportunities: Using Research to Accelerate the ...
(Date:12/8/2016)... ... December 08, 2016 , ... ... “Natural Language Processing–Enabled and Conventional Data Capture Methods for Input to Electronic Health ... . , Results of the comparative usability study demonstrate that a dictation-based method ...
(Date:12/8/2016)... ... December 08, 2016 , ... Mirixa Corporation , a ... other pharmacist-delivered patient care services, has announced the promotions of Karen Litsinger to ... president of sales. , Litsinger joined Mirixa in 2008 after serving as ...
(Date:12/8/2016)... ... ... With the increasing demand for dental implants, the National Association of Dental ... dentists and patients about the safety issues related to dental restorations. According to the ... is projected to reach $6.4 billion in 2018 with more than 30 million Americans ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... QUEBEC CITY , Dec. 8, 2016 /PRNewswire/ ... key US patents for improving the accuracy, reproducibility ... CD images in long and small bone orthopaedic ... proprietary approach to creating personalized orthopaedic restorations based ... create personalized orthopaedic restorations, the company harnesses the ...
(Date:12/8/2016)...  A new study by a pair of Geisinger ... therapy to treat chronic pain is not only ineffective, ... consequences, including death. Palliative care physicians ... , M.D., authored the study which provides a review ... study was published in the December 2016 edition of ...
(Date:12/8/2016)... Information products and services provider Elsevier has launched ... world,s largest abstract and citation database of peer-reviewed literature, providing the ... 5,000 publishers. The new set of metrics will improve decisions on ... adjust a journal,s editorial strategy. ... , CiteScore metrics comprise ...
Breaking Medicine Technology: