RNA Viruses

The structure of the RNA viruses is basically the same as that of the other viruses that we have described - a core of genetic material, usually contained within a protective capsid of protein, and in many cases, and lipid envelope as well. The life cycle of the RNA viruses is also similar - attachment to the host cell, penetration, reproduction of genetic material, creation of the protective capsid, emergence from the cell. The major differences arise from the fact that the RNA viruses genetic information is stored, as their name suggests, in RNA, not DNA. This has important consequences in the life cycle of the virus - and gives it the potential to outwit the immune system.

With the exception of the RNA viruses, all organisms store their permanent information in DNA, using RNA only as a temporary messenger for information. In part this has to do with the characteristic advantages of the DNA molecule and its replication. DNA is quite a stable molecule, not particularly reactive with other molecules, and the processes involved in its replication make very few mistakes during copying (between one in 1 million and 1 in 10 million). Most of these mistakes are normally corrected even when they do occur. This makes DNA an ideal format for the storage of information, for mutations (errors) only rarely occur, and most are not significant.

By contrast, RNA is a quite unstable molecule, capable of reacting even with itself under the correct conditions. It also makes frequent mistakes during copying - averaging one mistake per 10,000 nucleotides each time it is copied, and has less of an ability to correct errors. Since in normal cells RNA molecules are not "blueprint" quality, the host cell does not check copied RNA as carefully as it does DNA to assure that it is free of errors. These properties make RNA very poorly suited for the storage of information - which explains why all other organisms use it only as a temporary messenger molecule.

However, these very properties make RNA ideal for the storage of viral information. Once the immune system has learned to recognize an infecting virus and create antibodies against it (developed an immunity), it can quickly destroy it, so the virus can no longer use that host for reproduction. In order to reinfect that host - it must first change its nature enough that the immune system will no longer recognize it. In other words, it must mutate.

The unstable nature of the RNA molecule provides this mutagenic factor, allowing RNA viruses to evolve far more rapidly than DNA viruses, frequently changing their surface structures. These mutations make it more difficult for an organism to develop any kind of lasting immunity to the virus.

Micrographed stages of an RNA virus budding at the cell membrane

The structure of a typical "antisense" RNA virus - in this case, influenza A

Electron micrograph of influenza A viruses

Because each surviving virus can reproduce itself hundreds or thousands of times, mutations in the RNA sequence occur frequently. It has been estimated that a typical RNA virus may experience alterations of between .03 and 2 percent of its entire genome each year - evolving faster than any other living organism. Mutations occur randomly across the entire length of the viral RNA, and so of course most are not beneficial, producing viruses which lack a needed protein or are otherwise disadvantaged. However, because of the enormous number of offspring produced by each virus, even a high rate of mutation does not threaten the survival of the virus, and when advantageous mutations do occur, they are rapidly selected for and reproduced. This evolution is known as antigenic drift.

There are in fact two kinds of RNA viruses - those that have a "sense" strand of RNA (coded information about how to build proteins) as their genetic material, and those that have an "antisense" strand (the paired

opposite of the coded information). Hepatitis C is of the "sense" type.

In order to copy their genetic material, RNA viruses cannot rely on the mechanisms for genetic replication already present in the cell as the the DNA viruses do. Cells have their own DNA transcriptase (an enzyme which copies DNA) which they use to replicate their own DNA. DNA viruses can simply coopt this process to replicate their DNA. However, there are no instances where cells would ever replicate RNA - so the viruses are on their own. This copying of RNA is accomplished by a special set of enzymes that comprise an RNA transcriptase. The primary difference between the "sense" and "antisense" RNA viruses is where this RNA transcriptase comes from.

In order to express their genetic information, the antisense RNA viruses must first translate themselves into "sense" RNA - something which the host cell's ribosomes can read. Because the information is "antisense", there is no way for the virus to cause the cell to synthesize an RNA transcriptase - and so the virus must carry its transcriptase along with it. In some cases, it appears that these enzymes are packaged in the viral particle. This is true of the influenza A virus (the virus which causes flu), where many the needed enzymes are closely associated with the nucleic acid core of the virus. It must first transcribe itself to "sense" RNA that can be used as a template for the creation of new "antisense" viral RNA, and can also be read out by the cell's ribosomes to build viral proteins and so forth.

Sense RNA viruses, by contrast, have an much more powerful approach. Because their information is stored in a sense strand, the viral RNA itself can be directly read by the cell's ribosomes, functioning like the normal mRNA present in the cell. The virus thus needs to carry nothing with it. It uses the cell's own ribosomes to synthesize the RNA transcriptase it will need for reproduction, and once this is done, it creates an antisense version of itself as a template for the creation of new viral RNA. The new viral RNA can itself be used to synthesize more RNA's and the necessary viral proteins. The fact that their genes can be directly read by their host cells means that these types of RNA viruses are incredibly simple, requiring only small amounts of genetic material to encode the information necessary for their survival, and requiring no additional enzymes to be packaged into their cores. Some of our most deadly viral enemies are of this type. Hepatitis C is such a virus.

There is one other significant subtype of RNA viruses which deserves mention here, simply for the elegance of the threat that they pose. These are the retroviruses.