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.