Mouse virus study may offer HIV insights

30 October 2014

Electron micrograph of murine leukaemia virus-like particles containing a defective p12 protein.

Image: Electron micrograph of murine leukaemia virus-like particles containing a defective p12 protein.

Scientists have made an exciting inroad into understanding how a mouse retrovirus, murine leukaemia virus (MLV), forms a stable 'viral core' - the central part of the virus that contains its genetic material - and how this allows the virus to infect a cell.

It's hoped that understanding more about the properties of retroviral cores will lead to new treatments for retroviruses (which include human HIV) by targeting the stability of their viral core. The research was carried out by a team at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) and colleagues at Tel Aviv University in Israel.

Dr Kate Bishop of NIMR explained: "Retroviruses are a family of viruses that can cause severe diseases, including HIV/AIDS and cancer in humans.Innovative therapeutics for retroviral diseases will hopefully arise from a better understanding of how retroviruses reproduce in the cell, how they interact with host cell factors and how they affect the host immune system."

The genome of all retroviruses contains a gene called gag that codes for a large protein. This protein is cut into the individual proteins that are needed to form a new virus particle during replication. The proteins released include one called capsid, which forms a shell around the viral core and protects it. During replication, this shell falls apart (called 'uncoating'). The timing of this uncoating is critical for the virus to infect a new host cell.

In the MLV retrovirus, when the Gag protein is cut up, an additional protein named p12 is released, which is required for both early and late stages of the viral life cycle. However, it's role during early stages was not previously understood.

To investigate, Dr Bishop's team used a range of biochemistry and virology methods, including studying 'virus-like-particles' grown in cell culture in the laboratory and using high resolution microscopy.

They discovered that the p12 protein binds to the capsid shell around the viral core and stabilises it. Mutations in p12 resulted in virus particles with abnormally shaped and unstable cores that weren't able to replicate.

Dr Bishop said: "Understanding how the mature retroviral core forms and how it disassembles during infection is important as this determines the infectivity of all retroviruses, including HIV.

"Altering core stability has recently become a new target for HIV treatments. However, we do not yet know the exact timing or trigger for uncoating or how cellular and/or viral factors influence capsid shell stability. This is something my laboratory are very interested in."

The paper, The N-terminus of murine leukaemia virus p12 protein is required for mature core stability, is published in PLOS Pathogens.

  • New knowledge about a mouse virus from the same family as HIV may help researchers in their quest for new treatments for HIV/AIDS, according to scientists from the Medical Research Council's National Institute for Medical Research. 
  • The team has discovered the role of a protein in murine leukaemia virus (MLV) called p12, which was previously not understood. The protein plays an important part in stabilising the core of the virus, which contains its genetic material, and enabling successful replication. 
  • The WHO estimates that 35 million people are currently living with HIV, with almost one in 20 infected in Sub-Saharan Africa, the worst affected region.