All my articles on virology are written by hand instead of learning and selling them now. I just want to verify whether I can outline the main framework of virology from memory alone. Because it is written by hand, there are no references. Please ask colleagues or graduate students to correct it.
Today is the last part of the trilogy of viral replication, transcription and translation: the translation of viral proteins. I have always felt that RNA viruses are more interesting than DNA viruses because RNA viruses are unstable and come in many types. There are also many variations on copying, transcribing and translating. The same goes for translation. DNA viruses are nothing more than DNA→mRNA→protein, which is translated in a more traditional way.
But RNA viruses are different. Some viruses start with mRNA. There are many examples of this, such as Picornaviridae, Flaviviridae, etc. Although this kind of mRNA has a monocistronic structure, one cistron contains multiple structural and non-structural protein sequences. This mRNA is translated into a long polyprotein, which is then hydrolyzed layer by layer, and finally Forms structural and non-structural proteins. Interestingly, some of these viruses, which start out as mRNA, do not contain a 5' cap structure. If you have a solid foundation in biochemistry, you should know that the ribosome subunit must find the cap structure and then combine with it to initiate translation. . But like the foot-and-mouth disease virus, there is no hat structure. What should we do? There is a structure called the internal ribosome entry site (IRES), which just replaces the cap structure, binds to the ribosome and initiates translation. There are 5 types of IRES, mainly depending on the secondary structure of the RNA.
During the process of protein translation by ribosomes, there is another interesting phenomenon, which is ribosome skipping, which is very interesting. To put it bluntly, the ribosome slides along the mRNA. When it encounters a special sequence, it will "snap" (rather than terminate). The previously translated polypeptide chain falls off from the ribosome, and the ribosome continues to slide along the mRNA to translate the protein. . Isn't it interesting? Many members of the Picornaviridae family share this characteristic.
Another interesting phenomenon is the ribosome shift effect, which is divided into negative shift or positive shift (it should be called that, I can’t remember), that is, the ribosome moves along the The mRNA slides normally, encounters a special sequence, and then "bang" backwards or forwards one nucleotide position, and then continues to be translated, which causes the subsequent translation of the amino acid sequence to be completely disrupted. Two typical representatives are coronaviruses (negative shift) and influenza viruses (positive shift). Ribosome translocation effect, my memory is a bit fuzzy, please correct me.
I just talked about two very interesting examples of naughty ribosomes. When the ribosome slides along the mRNA and encounters a stop codon (UAA, UGA, UAG), translation will be terminated. The newly translated protein is shed from the ribosome and then undergoes further processing, such as acetylation, glycosylation, disulfide bond formation, higher-order structure formation, multimerization, etc., to become a mature protein.
By the way, one more thing. For some time in the past, I have always mistakenly thought that prions are the process of protein replication. In fact, this is completely wrong. The essence of a prion is that a certain protein undergoes a conformational change, usually from an α helix to a large number of β sheets, thus forming a prion with neurotropic properties. Hey, I'm a little sorry for my two doctoral supervisors. Both gentlemen used to be experts in prion research.
That’s all. The trilogy is over. From now on, it’s time to write about how viruses invade cells and what bad things they do inside them.
? 2020-03-17
F. Liu