FLU replication graphic: illustration of the life cycle of influenza virus

Above: illustration of influenza virus life cycle or replication. Image measures 500 pixels across, original image is 2744 pixels across. See all RKM flu images

SHORT EXPLANATION: At upper right, a virus particle lands on the cell surface and is then taken into the cell. The genetic information of the virus is released into the cell and heads for the cell's nucleus (where the cell's genetic information is housed). From the nucleus, the viral genes direct the production of new viral components. These collect together at the cell surface and form themselves into new virus particles. The newly forming virus particles bud from the cell and are released to infect other cells.
LONG EXPLANATION: At upper right, an influenza virus particle is shown landing on the cell surface. The virus docks with cell membrane when the red spikes (haemagglutinin) link to molecules on the cell surface. The cell surface folds inwards causing the virus particle to sink into the cell. The virus sinks deeper into the cell until it is completely wrapped up in cell membrane. The resulting membranous "bubble" (or vesicle) breaks free from the surface of the cell and transports its contained virus into the cell. The netlike structure beneath the docking virus and the whitish halo around the resultant vesicle represent clathrin, a protein that forms an external scaffold that causes the cell membrane to invaginate and finally form the vesicle. The clathrin coat is then lost and the virus in its naked vesicle can be seen half out of frame at the right of the image. The engulfed virus then appears in an endosome (the large irregular yellow vesicle at middle right). It is more acidic in the endosome and this modifies the haemagglutinin spikes. The altered haemagglutinin draws the membranes of the virus and endosome together and they merge, creating a hole through which the viral contents are poured into the cytoplasm. These contents include the viral matrix protein, M1, (purple) and the nucleocapsid (green helix). Some matrix protein is shown travelling to the nucleus. The nucleocapsid segments, which contain the viral genetic information, migrate to the nucleus. They move into the nucleus via nuclear pores (the flower like structures on the curved surface of the nucleus) and so deliver the viral genome to the nucleus (which contains the cell's own genetic material). In the nucleus, the viral genetic material (-ve sense RNA) produces viral messenger RNAs of various kinds (vmRNA) which travel out through the nuclear pores. (Messenger RNA, or mRNA, carries the genetic information that is used to direct protein maunfacture.) Some vmRNA directs the synthesis of nucleoprotein (green dots) that travel back into the nucleus. Other vmRNA directs the production of matrix protein (purple dots) shown emerging from a viral polyribosome (several ribosomes strung together along a length of viral mRNA) in the middle of the picture. Some matrix protein travels to the nucleus and some collects beneath the cell membrane. Other vmRNAs direct the production of external (transmembrane) viral proteins. The manufacture of such "external" proteins follows a different route. Production starts in the rough endoplasmic reticulum and progresses through the Golgi apparatus. The haemagglutinin (red) is shown progressing through the Golgi at lower left, finally being discharged onto the cell surface from a vesicle (the sphere containing red dots that is delivering its contents onto the cell surface through a hole). The neuraminidase (yellow) is shown (for clarity) going through the Golgi in parallel but above the haemagglutinin. In the nucleus, the viral -ve sense genome also produces full length +ve sense copies of itself. These are then used to create further copies of the viral genome. These new -ve sense viral genomic RNAs become associated with nucleoproteins and some matrix proteins that have migrated into the nucleus. Such newly formed nucleocapsids and their associated M proteins exit the nucleus via nuclear pores (the trail of green ribbons progressing across the picture that exit from the lowermost nuclear pore). Just beneath the cell surface, these individual ribonucleoprotein segments are shown associating together to form the helical nucleocapsid (the green barrel-like structure). Around the new nucleocapsid, the matrix proteins are shown collected beneath the cell membrane (the haze of purple particles marked M1), while above the cell membrane, haemagglutinin and neuraminidase have coated the surface. With all these viral elements now in place, the newly forming virus particle can begin to take shape and to bud from the cell surface. The cell membrane that envelopes the emerging nucleocapsid and matrix protein becomes the viral envelope (complete with projecting spikes) and the virus particle is released. The new virus particle is now ready to infect another cell. Although all these processes are shown occurring simultaneously they actually vary with time and various mechanisms operate to regulate the phases of the life cycle. The life cycle of influenza is rather complex and for more information, please check the references below:

FOR INFORMATION ON VIRUSES ENTERING CELLS please see virus entry into animal cells from Ed Rybicki.

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