Severity of a Patient's AIDS May Depend on Partner's Immune System

Certain Immune Systems Create Weakened HIV

by Dr. Barry Starr, Stanford University

March 28, 2008

When a person is infected with HIV, he or she usually goes on to develop AIDS. But not everyone gets there at the same speed. And not everyone's AIDS is the same.

Some people's symptoms are less severe and take longer to develop. A new report suggests that one reason for this might be who the AIDS patient got the infection from.

Certain immune systems can end up selecting for weaker versions of HIV. If someone gets infected from someone with that sort of immune system, then they will get a weaker form of HIV.

What the study found was that if someone is infected one of these weaker viruses, his or her AIDS is of a milder type. And that even after the HIV reverts back to a stronger version, the disease still progresses more slowly. More work will need to be done to confirm this last part.

The study did not directly test the original people's immune systems. But the researchers were able to see that the virus had traveled through someone with a certain immune system by looking at the DNA of their virus. There was a genetic "footprint" of where the virus had recently been.

To understand how they did their study, we need to go into a little more detail about how our immune system works. And why an immune system can select for weaker versions of HIV.

Bloodhounds and T cells

Killer T cells are like killer bloodhounds.
They sniff out infected cells and
destroy them.

An immune system is made up of lots of cells whose job it is to recognize and kill off invaders. One important player that has a lot to do with the recent study is called a killer T cell. Its job is basically to find cells that have been infected or aren't working properly and to destroy them. Think about killer T cells like bloodhounds.

Bloodhounds are dogs that police use to find bad guys. Sort of like our bodies use T cells to find infected cells.

A bloodhound has an incredibly sensitive nose that can recognize subtly different mixes of chemicals. The nose is so sensitive that from just a sniff of something a criminal left behind, a bloodhound can search out and find the criminal.

Killer T cells work similarly. Basically they "sniff" the outside of cells and can tell if it has been infected or not. If it has, the T cell kills the infected cell.

An important difference between bloodhounds and T cells has to do with what each can sense. A blood hound can tell the difference between lots of different chemicals and find the bad guy's combination. Its nose can detect many, many different chemicals.

Each kind of T cell can only sense one piece of a protein. Luckily we have lots of different kinds of T cells that can all detect different protein pieces so we can sniff out a wide range of invaders. Basically we have millions of bloodhounds that can each sense only one thing.

Here's a simplified version of how a T cell works. When a cell gets infected, it chops up the invader's proteins. The cell then sticks the bits of protein on the outside of itself. If a killer T cell recognizes the protein, it latches onto the infected cell and kills it.

Each person has a slightly different set of these T cells so we each recognize different bits of proteins. It is these differences that explain why who a patient gets his or her HIV from might determine how fast the patient's AIDS progresses.

Compromised HIV

When HIV invades a cell, it makes at least 15 different proteins. An infected cell chops these proteins up and displays them on the outside of the cell. A T cell then comes along and destroys the infected cell. Except when it can't see any foreign protein.

Remember, everyone's T cells recognize a different set of protein bits (or epitopes). And HIV is amazingly good at changing itself to evade these T cells.

Basically what HIV does is make lots of new versions of itself whenever it infects a cell. It makes so many that some of the viruses make no protein bits the T cells can recognize. Then the best of these new viruses wins out and the infection progresses.

But not all of these viruses are created equal. Some have to compromise their abilities to infect or make new copies of themselves to evade someone's T cells. These viruses don't progress to AIDS as quickly as other types. And these are the viruses that the group from South Africa studied.

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HLA Genes and the Immune System

A person's immune system is dependent on their genes. The ones we're interested in here are called the Class I HLA* genes.

These genes make proteins called HLA proteins. These proteins are like little holders for the specific protein bits that killer T cells recognize.

When a virus' proteins are chopped up into bits, they are displayed on the outside of the infected cell by these HLA proteins. Each HLA protein can hold a specific piece of a protein. So the viral proteins our T cells can recognize are determined by the protein bits these MHC proteins can hold.

It was known before this study that people with two specific HLA gene versions, HLA*57 and HLA*5801, end up with weaker forms of HIV. This is because these HLA genes target a particularly important part of an HIV protein called gag.

Viruses can successfully infect people with HLA*57 and HLA*5801 genes only by having mutations in the gag protein. And this causes the virus not to be as effective.

In fact, previous studies had shown that once these mutated viruses infect someone lacking these two gene versions, the virus eventually reverts back to a stronger form. This study investigated what the AIDS progression looked like before and after the reversion happened.

*HLA stands for Histocompatability Leukocyte Antigen

Weaker Virus, Slower Progression to AIDS

Some immune systems
create weaker forms
of HIV.

A common way that HIV gets around the HLA*57 and HLA*5801 gene versions is through specific mutations in the gag protein called T242N and A146X. These researchers looked at how AIDS progressed in HLA*57 and HLA*5801 negative people infected with viruses that have the T242N and A146X mutations.

They followed nine of these people from 62 days to 15 months post infection. What they found was that the disease progressed in these folks much more slowly compared to versions of HIV that did not have the mutations.

These people had higher CD4+ counts which means their immune systems functioned better. And they had lower viral loads which means their blood had fewer viruses.

The researchers were able to show that this didn't happen because the nine people happened to share similar HLA genes. It could be that certain HLA gene versions just lead to slower AIDS progression and it had nothing to do with the HIV mutations. This doesn't appear to be the case.

The researchers found that consistent with previous studies, the mutant viruses started to be replaced by stronger viruses. What is interesting is that there wasn't any real increase in viral load or decrease in CD4+ cells long after the reversion. In other words, these people may have a weaker form of the disease even after the virus mutates back to a stronger form.

It is important to note that the researchers don't know for sure that these viruses came from HLA*57 and HLA*5801 positive people. They have a lot of circumstantial evidence and go to great lengths to find signs that the viruses came from HLA*57 and HLA*5801 positive people. But they don't know for sure.

What they can say is that the viruses with these mutations lead to slower progression of AIDS at early stages. An important finding in its own right.

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Content provided by the Department of Genetics, Stanford University.