RW Malone MD@RobertMaloneMD

Coronaviruses and other single stranded RNA viruses are classified as positive or negative stranded depending on the polarity of the RNA. One can think of RNA polarity as sort of like reading a sentence from left to right (positive polarity) or right to left (negative polarity). The machinery in cells that makes proteins from RNA reads the RNA (message) from left to right. So, getting really technical, coronaviruses are a type of positive-polarity single-stranded enveloped RNA virus, which is to say that virus proteins can be produced directly from the RNA genome by reading it from left to right. The RNA does not have to go through another round of replication (as is required for negative-polarity RNA viral genomes) to get back to a form that can be read from left to right to produce proteins after infecting a cell. At a practical level, this also means that the RNA genome of a coronavirus can be infectious; the RNA alone, if transferred into a cell, can cause that cell to produce complete and infectious new coronaviruses. This is why mRNA vaccines only use a fragment of the mRNA genome, so that the mRNA can not reproduce virus.

Using RNA as the genetic material is very efficient (a single strand is easier and cheaper to make than two!), but it is also very likely to develop errors during replication relative to using double stranded DNA (like human beings use). Among other problems with this viral strategy is that this means that viruses that use RNA often mutate very fast. Good thing that human beings use DNA to store their genetic information!

RNA viruses make this high mutation rate work for them. The high mutation rate of RNA viruses is one reason why it is difficult to make effective vaccines against many of these types of viruses.

Positive-sense RNA viruses account for a large fraction of all known human viruses, including many well-known pathogens such as HIV (the AIDS virus), hepatitis C virus (liver cancer), rhinoviruses (common cold), West Nile virus, Dengue virus, Zika, SARS and MERS coronaviruses, and COVID-19. Even though the single stranded RNA strategy comes with the problem of high mutation rate, these viruses replicate so efficiently, and produce so many viruses so fast, that it does not slow them down. In fact, the high mutation rate is sort of an advantage for viruses- it makes it easy for them to evolve and adapt to a new host (you and me) very rapidly, and to adapt to escape immunity in the animals that they infect (including us).

There have been reports of the virus’ genome being different at various time points within an individual. Another RNA virus with this capability that we are all familiar with is HIV.

(For those of you paying attention, smash these ideas together with 1) escape mutants against a vaccine with a target of a single protein (spike in this case) and 2) why we don’t have a vaccine for HIV and the common cold…)

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