MadSci Network: Virology
Query:

Re: Please explain how H.I.V. has mutated from its time of discovery to today?

Date: Wed Jan 27 17:04:00 1999
Posted By: Brian Foley, Post-doc/Fellow Molecular Genetics
Area of science: Virology
ID: 916241689.Vi
Message:

The human immunodeficiency virus (HIV) has two major types called HIV-1 and HIV-2. We believe that HIV-1 came from chimpanzees to humans but don't yet know exactlty when this happened, maybe as long as 200 years ago but maybe as recently as 1940-something. HIV-2 seems to clearly have come from Sooty mangabey monkeys to humans, with at least 5 different monkey-to-human transmissions. There may have been several chimpanzee- to-human transfers of HIV-1, but it seems that only one of them gave rise to the current HIV-1 epidemic. As far as I know nobody has even tried to date the Sooty mangabey to human transfers.

The virus was not discovered until the early 1980s after people in the USA and Europe started dying of an immunodeficiency syndrome. SInce then we can see that the envelope gene of HIV-1 evolves at about 0.5% per year, whether within one single patient, or in the population as a whole. The pol gene evolves at about 0.25% per year. The rate of evoltuion is the rate of mutation minus the rate of selection. Mutations that are bad for the virus don't survive long. Most mutations in the pol gene are bad for the virus and are selected against. Some mutations in the env gene are good for the virus by helping it to evade the host immune system, so they are actually selected for (the mutant lives fine, while the "wild type" is being killed off by the host).

Anyway, with a rate of 0.5% per year and 26 years since the first HIV-1 virus was sequenced, you might think that viruses today would be 13% different in env from that first virus, and this is pretty much true for those viruses which are direct descendants from the early virus. However, this does not go on forever. Two hundred years from now we cannot have virus that is 100% different. Any two senquences at random are 25% identical because there are onely 4 DNA bases (A, C, T and G). On top of that, the selection tends to weed out the same mutations over and over while allowing some of the same ones over and over. Some sites will always remain as "T", while other sites go from "T" to "A" and back to "T" and then to "C" to "G" and back to "T" again. Mutations happen pretty much at random. The result is that the distance from the original sequence does not increase linearly with time. It has a curve, which tends to have a maximum value. The maximum divergence for the env gene might be something like 50%, while the maximum for the pol gene might be 20%.

Also, not all viruses out there today are descended from the virus that was sequenced in 1984. The virus has been in the USA and Europe since at least 1976, and had been in Africa for as much as 200 years. The total global diversity of HIV-1 may be close to saturation. The HIV-1 that is common in the USA and Europe is called HIV-1 subtype B. There are at least 7 other subtypes of HIV-1 that are related to the B subtype and placed in the "M group". On top of that there is an "O group" and an "N Group". Sometimes a virus from one subtype and a virus from another subtype infect the same person and recombine, producing a recombinant virus. The virus that is most common in Thailand is recombinant between A and E subtypes. A virus that is rapidly spreading in the former Soviet Union is recombinant between subtypes A and B.

We have found one blood sample, stored in a freezer since 1959, that was infected with HIV-1. That virus seemed to be close to the common ancestor of the subtypes B and D. So if we look at the distance between B and D subtypes today (about 16% in the env gene) and the distance between all subtypes (about 22% in the env gene) we can estimate that these viruses all shared a common ancestor about 60 years ago, but that is a fuzzy estimate because we don't know the curve of the distance vs. time line exactly. We just know that it is not straight. And with such a curved line the longer you go out in distance, the less accurate is your estimate of the time.

The idea for controlling this virus is to look for parts of the genome that do not evolve so fast. It is hard to hit a moving target. We look for regions of the genome that are the same in all the groups and subtypes of HIV-1 and maybe even the same in HIV-2 and the monkey viruses. That tells us that these regions are probably always going to remain unchanged and we can develop vaccines or drugs that will "hit" these regions.

The study of the evolution of HIVs and SIVs (simian immunodeficiency viruses from monkeys, apes and chimpanzees) is teaching us a lot about evolution in general. They evolve so fast that we can actually see the changes. They have tiny little genomes and they are viruses, so they don't have big physical changes to look at like a giraffe's neck, but viruses and all known life forms use DNA for their genes, so we can study how it changes over time. The SIVs don't seem to make their natural hosts sick. So there are theories about virus/host co-evololution that predict that HIV will eventually evolve to become harmless to humans over the next few thousand years. But nobody wants to wait even a few hundred years for this type of natural "cure". The theories do not predict what percentage of the host population will be killed off before the rest of the population is "immune" (not immune to infection, but immune to the damage done by infection), or the virus evolves to be less harmful.

Brian Foley, Ph.D.
HIV Sequence Database


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