Unlike more traditional vaccines, RNA-based vaccines are also beneficial in that they eliminate the need to work with the actual virus. Adam Fenster. Maquat has been studying RNA since and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.
Instead, the virus N protein seems to promote the pathway. Most people living in the United States today have only read about the flu pandemic and the relatively recent RNA viruses, such as Ebola or Zika, that are seen largely in other countries. Bats, in particular, are reservoirs for viruses. If these bat viruses mutate so they become capable of infecting humans, however, there will be new diseases, Maquat says.
The hope is that we will be ready and able to develop vaccines against these new viruses with the new pipelines that have been put in place for COVID This story was originally published on April 28, , and updated on December 14, Please consider downloading the latest version of Internet Explorer to experience this site as intended. Reoviruses are nonenveloped and particles consist of two or three concentric icosahedral capsid layers.
A unique feature of the reovirus replication cycle is that the genome segments are transcribed from within the capsid. The genomes of RNA viruses have some common general features.
Obviously there are one or more open reading frames that encode the viral proteins. But there are also regions of RNA that do not code for protein. These non-coding regions NCRs or untranslated regions UTRs are often highly conserved within a virus family, indicating that they have important functions. NCRs may have specific, critical nucleotide sequences but in some cases they are regions of the genome that fold into conserved structures, and structure may be more critical than a specific sequence.
Of course a source of RdRp must be supplied. RdRp may be encoded in the minigenome or may be supplied in trans by using a cell line stably expressing the viral RdRp, for example. The sequences required to direct RNA replication are often fairly simple and can be linked to virtually any RNA sequence to drive its replication.
These promoter sequences can be rather short but provide a means to direct the RdRp to internal sites on the genome. There may also be specific RNA sequences that signal polyadenylation. There are a variety of different strategies that RNA viruses use to regulate transcription and genome replication, but all involve RNA sequences found in the genome.
The RNA genomes of some viruses are highly structured and extensively base paired. The IRES serves as a platform for ribosome assembly. Promoters can be quite long and complex and promoter regions themselves are not transcribed. It is particularly important, in the case of genome synthesis, that genetic information not be lost or modified; however, mRNAs are often capped and polyadenylated. Are the methods for priming viral mRNA synthesis the same or different from the methods of priming genome replication?
The RNA viruses seem to have experimented widely. For example, the picornaviruses use poly A tracts encoded in the genome. Among the negative-strand RNA viruses, those in the order Mononegavirales use a stuttering mechanism to synthesize long poly A tracts from short poly U tracts Fig. A strategy to regulate mRNA synthesis. This figure shows the organization of a paramyxovirus genome paramyxoviruses are members of the order Mononegavirales ; negative-strand RNA viruses with unsegmented genomes.
Each protein-coding region is flanked by regulatory sequences that control capping and polyadenylation. The order of the genes on the genome regulates the relative quantities of mRNAs synthesized. Because RdRp does often dissociate from the genome during transcription, the downstream genes are produced in lower quantities.
Even with fairly simple genomes, RNA viruses must, and do, regulate the amounts of genome, copy genome, and mRNAs that are synthesized during an infection. It is much more efficient to synthesize many genomes from each copy genome. Internal promoters for mRNA synthesis can vary in sequence, controlling the relative affinity of the transcription complex for each mRNA.
An important feature of RNA viruses is that many exist in nature as quasispecies. The term quasispecies is used to describe a group of closely related, but nonidentical genomes Fig.
A Positive-strand RNA viruses exist as quasispecies, complex mixtures of related genomes. The mixture is more fit than any individual genome; fitness is maintained by generation of new variants in response to selective pressures.
B Potential for safer vaccines. If the fidelity of RdRp is increased the population remains more homogeneous. Therefore an attenuated virus with a high-fidelity RdRp is more likely to remain attenuated. Poliovirus PV is a good example of a virus that forms a quasispecies. If one examines genome sequences from a mouse experimentally infected with PV serotype 1, we find that the genomes are not identical, although they are all clearly related to one another.
To the surprise of many virologists, it turns out that the population quasispecies may be more fit than any individual genome. Or put another way, we cannot find any single genome in the population that replicates better than the group as a whole and in fact, most individual genomes replicate more poorly than the group.
Why this occurs is not always clear, but an animal is a very complex ecosystem. Different members of the quasispecies may be better adapted to different niches in the animal. How does a quasispecies form? But as the cloned virus replicates, mutations accumulate generating a quasispecies. Measurable levels of mutation occur because the fidelity of PV RdRp is low. RdRps do not have proof-reading activities as do many DNA polymerases. If a mistake occurs, there are only two possibilities: RNA synthesis can stop, or RNA synthesis can continue beyond the mistake to generate a point mutation.
A rate of one mutation per 10 5 nucleotides synthesized ensures that during an infection, many progeny will contain a mutation. Viruses may be simple. They may not even be alive, but they've been around a lot longer than we have. In fact, by the time humans arrived on the scene, about , years ago, viruses had already been doing their thing, infecting lizards and lemurs, trees and termites, for millions of years.
They probably evolve with life when life started in this planet. There've been there forever. We don't know exactly where they come from, but there are a lot of theories what they could potentially come from. But in any case, that's why they have that ability in the sense that because they're so evolved so independently with life in general, that they have the ability to go in and steal all these machinery.
They already know that it's there. So it's really a very fascinating mystery because we don't know exactly what was first, the chicken or the egg. So was first life on earth and then viruses came from that life?
Or viruses were first and then something happened that created something more sophisticated, like a life cell. There are a lot of theories. There's even from the s, people were talking about an RNA world where the very first signs of life in this planet was based on RNA and if that's true, maybe viruses was one of the first things that remember resemble some of the things that is alive, but it's not.
So maybe it should come as no surprise that viruses are as resilient and diverse as they are. They got a huge headstart. But just how diverse our viruses really?
It's part of the coronavirus family, which got its name because under a microscope, a coronavirus looks a little bit like a spiky crown. It's a vast family. In terms of scale, don't just imagine a Thanksgiving dinner table, imagine a family reunion that takes over a park and spills into the parking lot.
They are hundreds if not thousands of coronaviruses effecting different animals. There are several studies showing that they are coronaviruses that can affect pigs and cows and cats and bats.
And there are probably thousands of them. And the last literature that I checked actually says that there are probably around a thousand coronaviruses already been found in bats.
Now from all that, a huge amount of viruses are limiting other organisms that could potentially jump to human. That is called a spill over. That's when a virus that is in an animal actually is able to infect humans. There's only been actually seven coronaviruses as far as we know that infect humans. Actually the first two coronaviruses were discovered in the s and the other two were discovered around , And that was the sixth virus that we know of infections.
And that's just the coronavirus family. If you start to consider other virus families, the scale becomes staggering. Millions of virus types have permeated every ecosystem on earth.
There are rhinoviruses which cause the common cold and influenza viruses, which cause the flu. There are viruses that are infect humans and viruses that infect other animals and plants and insects and even bacteria. Some viruses have DNA the way we do. Instead their genomes are made of RNA.
So if we talk about RNA in general, when they teach you your classes of molecular biology when you go to high school or even college, they, for many, many decades, people always thought that RNA was just kind of like a transitional molecule.
We always believed that was kind of, it was called the dogma biology, the dogma of molecular biology. That means that our information, our genetic information is in the DNA. And then RNA was some sort of a messenger molecule that was taking this information from DNA to another part in the cell to make proteins. And that was really the only function at that time, people believed that was it.
Of course now we know that is not true. RNA is very important. Not only for that type of job inside the cell to send information from one place to another, but now we know that RNA has so many other functions, so many, so many is from, they have the ability to work like an enzyme. They have a catalytic activity, they can be like a genome. Like we've been talking about coronaviruses. So RNA is a very flexible molecule that can not only contain genetic information, but also can have a function as an enzyme, as a messenger, and as a regulator of other RNAs and other proteins.
So now we start to understand the importance of RNA, not only in any type of organisms and human diseases, but also in a viral infections. These vaccines that we are trying to develop, or people are trying to build right now, there is like a super fast track type of vaccines.
It is a very interesting type of technology they're using right now to develop these vaccines as fast as they can. So when people said we would not going to have a vaccine in a year, year and a half, people think that, oh my God, that's a long time.
In reality, that's a very fast developing of vaccine. Developing a type of vaccine, like I said, takes many, many years. This is a completely different type of technology they're using. They actually, they're talking about RNA. They use fragments of RNA from the virus, some of these industries, there's some of these places they're trying to develop the vaccine. They're using fragments of this RNA from the virus and put them artificially in cells.
So they can actually make proteins of the virus without having the whole virus entirely. So it's very safe and they're trying to find it as accurate as possible. So they can develop a very unique antibodies, a vaccine that could develop antibodies specifically for the virus.
And that way you can administrate these vaccines very fast. And it doesn't take that long compared to a traditional way of making vaccines. That, like I said, it takes too many, many years. Another vaccine candidate that has been gaining attention in the news was developed by the University of Oxford in England. That vaccine is a little different and is already entering advanced trials of its own.
0コメント