Improving Health & Medicine

Weizmann Institute Scientists Reveal the Invasion Strategy of the World's Largest Virus

• News Release • TAGS: Biology, Chemistry, Medicine, Virus

REHOVOT, ISRAEL—May 29, 2008A Weizmann Institute study provides important new insights into the process of viral infection. The study, reported in the online journal PLoS Biology, reveals certain mechanisms by which mimivirusa virus so called because it was originally thought to mimic bacteria in various aspects of their behaviorinvades amoeba cells.

Living cells become infected by viruses in two steps. First, the virus penetrates the cell. Next, in the second and crucial step, the cell starts producing new viruses, which spread and infect additional cells. At the beginning of this production process, the cell makes the outer wall of the virus, which is a container of sorts composed of proteins and known as the capsid. The cell then makes copies of viral DNA and inserts it into the capsid. The result is a new, functioning virus that is ready to leave the host cell and infect more cells.

Understanding how viruses infect cells and how new viruses are produced in the course of the infection allows scientists to interrupt the infection cycle, blocking viral diseases. One of the difficulties, however, is that the invasion strategies of different viruses greatly vary from one another.

The mimivirus, known, among other things, for its exceptional sizeit is five to ten times larger than any other known virusposes an interesting challenge in this respect. This virus was discovered only in the late twentieth century, as its extraordinary size made it impossible to identify it by regular means. In addition, it contains much more genetic material than other viruses, a feature that forces the mimivirus to develop particularly efficient methods for introducing its viral DNA into the host cell and for inserting the genetic "parcel" into the protein container during the production of new viruses in the host cell.

The Weizmann Institute's Prof. Abraham Minsky and graduate students Nathan Zauberman and Yael Mutsafi of the Department of Organic Chemistry, together with Drs. Eugenia Klein and Eyal Shimoni of Chemical Research Support, have now revealed the details of some of the methods used by this virus. In their new study, the scientists have obtained, for the first time, three-dimensional pictures of the openings through which the viral genetic material is injected into an infected cell, and of the process by which this genetic material is inserted into the protein capsid.

In all previously studied viruses, viral genetic material was shown to be injected into the cell (during the cell's infection) and to enter the newly formed protein container (during the production of new viruses inside the cell) through the same channel, which was created in the viral container. In contrast, the Institute scientists discovered that the giant mimivirus uses a different channellocated in a different part of its capsidfor each of these two goals. The scientists also discovered that the DNA helix in both these processes does not form a long thread, as in other viruses, but rather is organized into a densely packed block. The researchers believe that these unique traits serve to specifically facilitate both the injection into the host cell and the insertion of the large quantity of genetic material in the mimivirus.

In the Weizmann study, electron microscope images of the mimivirus invading an amoeba cell showed that just after invasion, the walls of the protein capsida polygon composed of 20 trianglesseparate from one another and open up like flower petals to create a large, star-shaped entry nicknamed the "stargate." The viral membrane underneath the stargate fuses with the amoeba cell membrane, creating a broad channel that leads into the amoeba. The pressure released with the sudden opening of the wallswhich is 20 times greater than the pressure pushing the cork out of a Champagne bottlepushes the viral DNA into the channel, whose large dimensions allow the genetic material to pass quickly into the amoeba cell.

Additional images show how the viral genetic material is inserted into the newly formed protein container when new viruses are produced in the host cell. In this process, the viral genetic material is delivered to its destination through an opening in the new container's wall opposite the stargate. The insertion must overcome the pressure inside the container and is probably driven by an "engine" located within the wall that harbors the opening.

The scientists believe that the study of the mimivirus's life cycle, from cellular infection to the production of new viruses, may yield valuable insights into the mechanisms of action of numerous other viruses, including those that cause human diseases.

Prof. Abraham Minsky's research is supported by the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly. Prof. Minsky is the incumbent of the Professor T. Reichstein Professorial Chair.The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

Improving Health & Medicine

Weizmann Institute Scientists Reveal the Invasion Strategy of the World's Largest Virus

• News Release • TAGS: Biology, Chemistry, Medicine, Virus

REHOVOT, ISRAEL—May 29, 2008A Weizmann Institute study provides important new insights into the process of viral infection. The study, reported in the online journal PLoS Biology, reveals certain mechanisms by which mimivirusa virus so called because it was originally thought to mimic bacteria in various aspects of their behaviorinvades amoeba cells.

Living cells become infected by viruses in two steps. First, the virus penetrates the cell. Next, in the second and crucial step, the cell starts producing new viruses, which spread and infect additional cells. At the beginning of this production process, the cell makes the outer wall of the virus, which is a container of sorts composed of proteins and known as the capsid. The cell then makes copies of viral DNA and inserts it into the capsid. The result is a new, functioning virus that is ready to leave the host cell and infect more cells.

Understanding how viruses infect cells and how new viruses are produced in the course of the infection allows scientists to interrupt the infection cycle, blocking viral diseases. One of the difficulties, however, is that the invasion strategies of different viruses greatly vary from one another.

The mimivirus, known, among other things, for its exceptional sizeit is five to ten times larger than any other known virusposes an interesting challenge in this respect. This virus was discovered only in the late twentieth century, as its extraordinary size made it impossible to identify it by regular means. In addition, it contains much more genetic material than other viruses, a feature that forces the mimivirus to develop particularly efficient methods for introducing its viral DNA into the host cell and for inserting the genetic "parcel" into the protein container during the production of new viruses in the host cell.

The Weizmann Institute's Prof. Abraham Minsky and graduate students Nathan Zauberman and Yael Mutsafi of the Department of Organic Chemistry, together with Drs. Eugenia Klein and Eyal Shimoni of Chemical Research Support, have now revealed the details of some of the methods used by this virus. In their new study, the scientists have obtained, for the first time, three-dimensional pictures of the openings through which the viral genetic material is injected into an infected cell, and of the process by which this genetic material is inserted into the protein capsid.

In all previously studied viruses, viral genetic material was shown to be injected into the cell (during the cell's infection) and to enter the newly formed protein container (during the production of new viruses inside the cell) through the same channel, which was created in the viral container. In contrast, the Institute scientists discovered that the giant mimivirus uses a different channellocated in a different part of its capsidfor each of these two goals. The scientists also discovered that the DNA helix in both these processes does not form a long thread, as in other viruses, but rather is organized into a densely packed block. The researchers believe that these unique traits serve to specifically facilitate both the injection into the host cell and the insertion of the large quantity of genetic material in the mimivirus.

In the Weizmann study, electron microscope images of the mimivirus invading an amoeba cell showed that just after invasion, the walls of the protein capsida polygon composed of 20 trianglesseparate from one another and open up like flower petals to create a large, star-shaped entry nicknamed the "stargate." The viral membrane underneath the stargate fuses with the amoeba cell membrane, creating a broad channel that leads into the amoeba. The pressure released with the sudden opening of the wallswhich is 20 times greater than the pressure pushing the cork out of a Champagne bottlepushes the viral DNA into the channel, whose large dimensions allow the genetic material to pass quickly into the amoeba cell.

Additional images show how the viral genetic material is inserted into the newly formed protein container when new viruses are produced in the host cell. In this process, the viral genetic material is delivered to its destination through an opening in the new container's wall opposite the stargate. The insertion must overcome the pressure inside the container and is probably driven by an "engine" located within the wall that harbors the opening.

The scientists believe that the study of the mimivirus's life cycle, from cellular infection to the production of new viruses, may yield valuable insights into the mechanisms of action of numerous other viruses, including those that cause human diseases.

Prof. Abraham Minsky's research is supported by the Helen & Milton A. Kimmelman Center for Biomolecular Structure & Assembly. Prof. Minsky is the incumbent of the Professor T. Reichstein Professorial Chair.The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.