Poliovirus, a member of the family Picornaviridae, is a contagious virus that invades the nervous system and can cause paralysis. It is transmitted through contaminated food or water, or through contact with an infected person. The virus enters the body through the mouth and multiplies in the intestine. It then spread through the bloodstream to the nervous system.
The virus attacks the central nervous system, which consists of the brain and the spinal cord. The virus enters the neurons, or nerve cells, and multiplies. The virus hijacks the cell’s machinery, causing it to produce more copies of the virus. The virus then spreads to other neurons, causing them to malfunction. This can lead to paralysis, or the inability to move, and sometimes death.
There is no cure for poliovirus, but there is a vaccine that can prevent it. The vaccine is made from dead viruses, and it is given to children in multiple doses. The vaccination program has been successful in reducing the number of cases of polio worldwide.
Although much is known about how poliovirus (PV) enters cells, less is known about how the virus sets up shop once inside. New findings from a team of Rockefeller University scientists shed light on how the virus takes control of certain cellular mechanisms to efficiently coax the cell into churning out more virus particles. The discovery could lead to new ways to stop the virus, which still affects children in parts of the world where routine vaccination is not possible.
PV belongs to a family of viruses called picornaviruses, which are among the simplest and smallest of all viruses. They are so small that they can only be seen with an electron microscope. The viruses are composed of a single strand of RNA, the genetic material that uses proteins to carry out its instructions, encapsulated in a sphere composed of proteins.
PV enters cells through a portal called an icosahedral vault. Once inside, the viral RNA is uncoated, or released from its protein shell, and begins to direct the cell to make new viral proteins. These new proteins self-assemble into new virions, or virus particles.
The cell can produce a limited number of these new virions before it becomes overwhelmed and dies. In order to produce enough new virions to cause an infection, PV must take control of the cell’s machinery and force it to produce more.
The Rockefeller team, led by Richard Plemper, head of the Laboratory of Virology and Infectious Disease, found that PV hijacks a cellular process called autophagy. Autophagy is a mechanism by which the cell disassembles its own components, such as damaged mitochondria, and recycles them for energy or to build new cellular structures.
PV uses autophagy to its advantage by co-opting the machinery that disassembles mitochondria. When a cell is infected with PV, the virus causes the autophagic machinery to target mitochondria for destruction. This has two effects: first, it frees up energy for the cell to use to make more virus particles; and second, it causes the cell to produce more of the proteins needed for autophagy.
The team also found that PV induces autophagy by activating a protein called Beclin-1. Beclin-1 is a key regulator of autophagy, and its activity is increased by PV infection.
Interestingly, the team found that Beclin-1 is not required for PV to enter cells, but is essential for the virus to take control of the cell and hijack autophagy. This suggests that Beclin-1 may be a potential target for new antiviral drugs.
The findings were published in the journal Nature Cell Biology.
