Understanding Viral Diversity

Why are there so many different versions of HIV?

Globally, more than 40 million people are infected with HIV. The vast majority of these people experience similar symptoms. Those people that have access to treatment have broadly similar responses to prescribed drug regimens, regardless of where they live. In these respects all HIV-positive people carry the same virus. But this does not mean that everyone is infected with an identical version of HIV. In fact there are many, many different versions of HIV. These can be thought of as members of a large family: they are different from, but related to, each other. The broad term for this phenomenon is viral diversity.

The usual way that researchers look at the differences between HIV strains is to examine the ‘genome’ or genetic code. All versions of HIV have similar but distinct genomes. Researchers can compare different HIV samples from different parts of the world using a technique called sequencing, which essentially "reads" the viral genome. The genome consists of a chain-like strand of building blocks called ‘nucleotides.’ There are four different nucleotides and long chains of these nucleotides make up a genome. The HIV genome contains all the information HIV needs to infect cells, make millions of copies of itself and cause disease. The sequence of nucleotides in a strand identifies the virus, like a fingerprint.

By sequencing pieces from thousands of viral genomes, researchers have been able to map out the "family tree" of HIV. At the root of the tree, there are three ‘groups’ called M, N and O. Group M is responsible for the current AIDS pandemic.

Where did these groups come from? The answer lies in the origins of HIV itself. HIV is a relative of a virus called SIV (simian immunodeficiency virus) found in non-human primates, like chimpanzees and monkeys. Researchers think that some time in the first half of the 20th century SIV was passed from a nonhuman primate to a human, perhaps through a bite from a chimpanzee or through eating ‘bushmeat.’ The virus crossed from one species (chimpanzee) to another (humans). It was able to adapt to the human body and became what is now called HIV. Animal-to-human transmission is thought to have happened several times in different locations. Today’s groups probably arose from these separate events of ‘cross-species transmission.’

Over time additional genetic diversity has developed within each group. Viruses in Asia have developed differently from those in Africa. These regional subgroups are called clades, or genetic subtypes. Viruses within the same clade have genetic sequences that are more similar to one another than they are to sequences from other clades. Group M is split into nine clades. These clades have geographic distribution patterns. Clade C circulates in South Africa, India and parts of China. Clades A and D are common in east Africa and clade B is common in North America and western Europe.

HIV diversity is still increasing due to several processes. One process is called mutation. HIV reproduces (or replicates) in an infected person by making more copies of its genome. When it copies itself it frequently makes errors, called mutations. Mutations are the main reason why each person’s viral population is slightly different, even from the HIV that he or she was originally infected with.

The other process, recombination, can happen if a person is infected with two different versions of HIV. It is possible for people who are repeatedly exposed to HIV to become infected with more than one virus—including viruses from different clades. (In some geographic regions there is a major clade plus smaller proportions of other clades.) Then these viruses can sometimes exchange portions of their genomes to form a new ‘recombinant’ virus that has parts of genes from each parent virus. Recombinant strains can be passed from one person to another. In some regions the major circulating HIV is a recombinant virus.

A problem for vaccines?

Viral diversity poses challenges for vaccine design. HIV vaccines are constructed using small pieces of the virus, called ’immunogens.’ When a person is given a vaccine, these immunogens are "seen" by the immune system. This causes an immune response that creates defenses against the pieces of HIV. The goal of an AIDS vaccine is to get the immune system to create strong defenses that stop infection or disease if the person is later exposed to the complete virus [HIV].

One key question is: will fragments from one clade cause immune responses that protect against other clades? The same question applies to viruses within the same clade that have mutated, and are now very different from the original virus used to make the candidate vaccine.

Vaccine researchers are trying a number of different strategies to address these questions. One approach involves making vaccines that are not based on a single virus. Instead hundreds of HIV genomes are compared and an HIV sequence is artificially created based on the most common features of all the genomes. The result is a ‘consensus’ HIV sequence that bears a closer genetic similarity to all the circulating viruses than does an HIV sample taken from a single person. Another approach is to make vaccines that include HIV genes from multiple different clades. For example, one candidate vaccine that is being studied includes HIV genes from clades A, B and C.

There is ongoing debate about how to best to organize, or classify, the different versions of HIV. For vaccine design it may prove more useful to organize HIV diversity using categories other than clades. One approach is to organize the different versions of HIV by the immune responses they cause in people. This is called organizing viruses by ‘immunotype’ and may give better clues about how to raise strong immune defenses against HIV.