Wednesday, February 24, 2016

New Images of Protein Structure Gives Insight Into HIV

 Salk researchers captured the structure of a protein complex called an intasome (center) that lets viruses similar to HIV establish permanent infection in their hosts. The intasome hijacks host genomic material, DNA (white) and histones (beige), and irreversibly inserts viral DNA (blue).
Credit: Salk Institute
Retroviruses like human immunodeficiency virus (HIV) operate by inserting their DNA into human DNA, making the previous human cell into a virus making factory. In other words, the retrovirus "hijacks" the host cell. A new study has illuminated the previously unknown structure of the intasome, the mechanism behind the virus that injects the virus' DNA into the host cell.

Previous work on the subject has been done on a virus called prototype foamy virus (PFV), since it is less tricky to study than the HIV virus. The HIV virus affects human immune cells with their intasomes, eventually leading to the death of the immune system. Salk researchers have done this latest study on mouse mammary tumor virus (MMTV), which is more closely related to the HIV virus than PFV. The team used cryo-electron microscopy (cryoEM), a technique that has certain advantages over older methods such as x-ray crystallography. Essentially, the researchers were able to freeze the virus and intasome in time using a frozen liquid solution, all while it was affecting the host cell. They were able to capture an image by measuring how electrons deflected off of the protein.
Previous studies on PFV showed that its intasomes were made of four protein components (called integrases) bound by two strands of viral DNA. This recent study has shown that MMTV has eight integrase molecules per two strands of viral DNA. This suggests that HIV may contain a more complex protein structure than previously thought and a different mechanism of entry than PFV. This new framework gives molecular biologists a greater insight into the possible mechanism of how HIV delivers its DNA into the human host cell. 

Overall, more sophisticated imaging techniques will allow us to see the structure of viruses and disease causing bacteria in greater detail. By having a greater understanding of structure, we will be able to make more informed and accurate descriptions of functions. If we know the shape and way in which lethal viruses like HIV move, we will have a much greater chance of curing the disease.


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