News: Latest – distributed around Yorkshire August 12, 2016 12:25:05 PM
Scientists from the MRC Laboratory of Molecular Biology in Cambridge and University College London have discovered an essential feature of the HIV virus that it uses to infect cells whilst avoiding detection by the immune system. This discovery, published in Natureopens in new window, presents a new drug target and the opportunity to re-evaluate existing treatments for HIV to improve their efficacy.
HIV is a retrovirus, meaning it has to copy its RNA genome into DNA in order to infect cells. Previously, it wasn’t known how the virus acquires the building blocks of genetic material it needs, called nucleotides. Importantly, it also wasn’t known how HIV does this without setting off the cells alarm systems that are poised to detect foreign DNA.
HIV is surrounded by a protein shell called the capsid. It has now been found that HIV hides within the capsid while it builds DNA. The interdisciplinary team used a hybrid approach that involved discerning the atomic structure of the capsid in different states and creating mutant versions of HIV viruses to see how this altered infection. This allowed the researchers to discover iris-like pores in the capsid that open and close like those in the eye. These pores suck in nucleotides needed for replication at great speed while keeping out any unwanted molecules. This helps to explain why HIV is so successful at evading the immune system.
After they identified these capsid pores the team then went on to design an inhibitor molecule that could block them – hexacarboxybenzene. Once the pores were blocked by the molecule, the HIV virus was unable to copy itself and became non-infectious.
Hexacarboxybenzene cannot cross the cell membrane of human cells to gain access to the virus, but the researchers suggest that drugs could be designed in the future with similar properties but able to enter the cell. Another option is to look at drugs currently used in treating HIV, called reverse transcriptase inhibitors, to see if there are ways of improving their transit through these pores thereby enhancing their activity.
Senior author, Dr Leo James at the MRC Laboratory of Molecular Biology said: “We used to think that the capsid came apart as soon as the virus entered a cell but now realise that the capsid protects the virus from our innate immune system. The channels we’ve discovered explain how the fuel for replication gets into the capsid to allow the viral genome to be made.”
Lead author, Dr David Jacques at the MRC Laboratory of Molecular Biology, said: “We have already designed a prototype inhibitor that directly targets the channel. We predict that this feature may be common to other viruses and will be an attractive target for new antiviral drugs, including new treatments for HIV and related viruses.”
Dr Tim Cullingford, Programme Manager for Chemical Biology at the MRC, said: “This collaborative work between Leo James’s laboratory at the MRC Laboratory of Molecular Biology, Cambridge and Greg Towers at UCL really illustrates the value of taking an interdisciplinary approach to discovery research. The combination of atomic-level structural work with virology has enabled them to make a finding that will shape the direction of future work in this area.”
- Boys to be dealt with for damage to Barnsley monument
- Barnsley ram raids
- Two jailed for hate crimes in Rotherham
- Rotherham drugs raid reveals £500k crop
- Russia sends ‘squadrons’ of nuclear-capable bombers to Crimea in response to U.S. missile shield in Romania
- Miners’ memorial plan in former pit village wins planning permission
- Graham Brady’s Amendment Passes
- Appeal: Aggravated Burglary in Rotherham
- UPDATE – Martin Shaw back behind bars
- Witnesses to Balby assault urged to come forward
- Charity’s plea to rescue centres
- Membership of the World Association of Zoos and Aquariums
- Rare Photo Hooton Roberts
- Chance to share memories of Barry
- Chloe’s pride at representing Team GBR
- A statement from Rotherham’s Director of Public Health, Teresa Roche
- Dental patient awarded £7,000 in compensation
- WANTED MAN! Aaron Divers?
- Power to be handed back to Rotherham council
- Wath Comp Bumper crop of A-Level results
- CCTV image released following assault in Barnsley
- Council rolls out more safety measures for schools
- Fatal collision in Barnby Dun Doncaster
- Welcome of CSE sentencing in first Operation Stovewood case
- Sheffield man behind bars for ‘ferocious attack’ on woman
- Children Playing On West Street 1900
- Pedestrian seriously injured in Doncaster collision
- Renewed appeal to trace teenager Olivia
- Rotherham Show 2018 – something for everyone!
- E-fit released in connection to a theft in Rotherham
- Highway Code rules updated
- Road networks targeted by Op Voyager
- Convicted paedophile pleads guilty to further sex offences
- Barnsley Market Parade to close for one day
- Echoes of the Pier: A Tale of Forgotten Waters
- CCTV released following burglary in Barnsley
- Full council to consider Community Poll on devolution path for Barnsley
- Rotherham trio wanted for crystal meth conviction
- On this day 9th October
- Wath Firm Metalysis lands deal with MoD laboratory