Target Health Blog

Evolution of Viruses

November 23, 2020


Two rotaviruses: the one on the right is coated with antibodies that prevent its attachment to cells, thus preventing infecting them. Photo credit: by GrahamColm at en.wikipedia, CC BY-SA 3.0; Wikipedia Commons

The origins of viruses in the evolutionary history of life are unclear: some may have evolved from 1) _____ -pieces of DNA that can move between cells - while others may have evolved from 2) _____. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity in a way analogous to sexual reproduction. Viruses are considered by some biologists to be a life form because they carry genetic material, reproduce, and evolve through natural selection, although they lack the key characteristics, such as cell structure, that are generally considered necessary criteria for life. Because they possess some but not all such qualities, viruses have been described as “organisms at the edge of life,“ and as self-replicators.

Viruses undergo evolution and natural selection, just like cell-based life, and most of them evolve rapidly. When two viruses infect a cell at the same time, they may swap genetic material to make new, “mixed“ viruses with unique properties. For example, flu strains can arise this way. RNA viruses have high 3) _____ rates that allow especially fast evolution. An example is the evolution of drug resistance in HIV.

The reason that a different strain of flu virus comes around every year, is that viruses evolve. HIV, the virus that causes AIDS, can become drug-resistant because viruses evolve. Virus evolution is able to take place because the “gene pool“ of a virus population can change over time. In some cases, the viruses in a population -such as all the flu viruses in a geographical region, or all the different HIV particles in a patient's body - may evolve by 4) _____ natural selection. Heritable traits that help a virus reproduce (such as high infectivity for influenza, or drug resistance for HIV) will tend to get more and more common in the virus population over time.

Not only do viruses evolve, but they also tend to evolve faster than their hosts, such as humans. That makes virus evolution an important topic, not just for biologists who study viruses, but also for doctors, nurses, and public health workers, as well as anyone who might be exposed to a virus, which is everyone. Natural selection can only happen when it has the right starting material: genetic variation. Genetic variation means there are some genetic (heritable) differences in a population. In viruses, variation comes from two main sources:

Recombination: viruses swap chunks of genetic material (5) _____ or RNA).

Random mutation: a change occurs in the DNA or RNA sequence of a virus.

Recombination usually happens when two viruses have infected the same cell at the same time. Since both viruses are using the cell to crank out more virus particles, there will be lots of virus parts - including newly made genomes - floating around in the cell at once. Both strains co-infect the same host cell and the segments get mixed up in the host cell. Under these circumstances, recombination can happen in two different ways. First, similar regions of viral genomes can pair up and exchange pieces, physically breaking and re-connecting the DNA or RNA. Second, viruses with different segments (kind of like tiny chromosomes) can swap some of those segments, a process called reassortment.

Influenza (“flu“) viruses are masters of reassortment. They have eight RNA segments, each carrying one or a few genes. When two influenza viruses infect the same cell at the same time, some of the new viruses made inside of the cell may have a mix of segments Human influenza virus and bird influenza virus infect same pig cell. Each has eight segments of RNA in its genome. The segments get mixed up as new viruses are made in the cell.

Pigs in particular are well-known “mixing vessels“ for influenza viruses. If a cell in the pig is infected with two types of virus at the same time, it may release new viruses that contain a mixture of genetic material from the human and bird viruses. This kind of swap is common for influenza viruses in nature. A well-known swap was the 6) _____ influenza strain (“swine flu“) that caused a pandemic in 2009. H1N1 had RNA segments from human and bird viruses, as well as pig viruses from both North America and Asia. This combo reflected a series of reassortments that occurred step by step over many years to produce this H1N1 strain.

Some viruses have very high mutation rates, but this is not universally the case. In general, RNA viruses tend to have high mutation rates, while DNA viruses tend to have low mutation rates. The key difference lies in the copying machinery. Most DNA viruses copy their genetic material using enzymes from the host cell, called DNA polymerases, which “proofread“ (catch and fix mistakes as they go). RNA viruses instead use enzymes called RNA polymerases, which do not proofread and thus make many more mistakes.

Case study: HIV drug 7) _____

Human immunodeficiency virus (HIV) is the virus that causes acquired immune deficiency syndrome (AIDS). HIV is an RNA virus with a high mutation rate and evolves rapidly, leading to the emergence of drug-resistant strains. Because RNA viruses like HIV have a high mutation rate, there will be lots of genetic variation in the population of HIV viruses in a patient's body. Many of the mutations will be harmful, and the mutant viruses will simply “die“ (fail to reproduce). However, some mutations help viruses reproduce under specific conditions. For instance, a mutation may provide resistance to a drug.

Evolution of drug resistance in HIV

Certain drugs can block the replication of HIV by inhibiting key viral enzymes. Taking one of these drugs will at first reduce a patient's viral levels. After a while, however, the HIV viruses typically “bounce back“ and return to high levels, even though the drug is still present. In other words, a drug-resistant form of the virus emerges.

Reverse transcriptase inhibitors bind to a viral enzyme called reverse transcriptase. The drug keeps the enzyme from doing its job of copying the RNA genome of HIV into DNA. If this enzyme is inactive, an HIV virus cannot permanently infect a cell. Most HIV viruses are stopped by 8) _____. However, a very small fraction of the viruses in the HIV population will by random chance have a mutation in the gene for reverse transcriptase that makes them resistant to the drug. For instance, they might have a genetic change that alters the drug's binding site on the enzyme, so that the drug is no longer able to latch on and inhibit enzyme activity. The viruses with this resistance mutation will reproduce despite the presence of the drug and, over generations, can re-establish the viral levels present before the drug was administered. Not only that, but the entire virus population will now be resistant to the drug!

If HIV can evolve its way around a drug, how can the virus be stopped? What seems to work best is a combination approach, with three or more drugs taken at the same time. This approach to treatment is called highly active antiretroviral therapy, or 9) _____ for short. The drugs given in a HAART “cocktail“ typically target different parts of the HIV lifecycle. The HAART approach works because it is relatively unlikely that any one HIV virus in a population will happen to have three mutations that give resistance to all three drugs at the same time. Although multi-drug-resistant forms of the virus do eventually evolve, multi-drug combinations considerably slow the evolution of resistance.

Viruses 10) _____ faster than humans

As in the case of HIV, some viruses have a high mutation rate, which helps them evolve quickly by providing more variation as starting material. Two other factors that contribute to the fast evolution of viruses are large population size and rapid lifecycle. The bigger the population, the higher the odds that it will have a virus with a particular random mutation (e.g., one for drug resistance or high infectivity) on which natural selection can act.

ANSWERS: 1) plasmids; 2) bacteria; 3) mutation; 4) natural; 5) DNA; 6) H1N1; 7) resistance; 8) nevirapine; 9) HAART; 10) evolve

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