'Badder' isnt 'Better': Recombination and Super AIDS

Some people have emailed me this story, concerned about the evolution of a 'recombinant' HIV virus that makes people progress to AIDS much faster than 'regular' HIV.

Scientists Find Aggressive New HIV Strain

This is the paper they are referring to:

Faster Progression to AIDS and AIDS-Related Death Among Seroincident Individuals Infected With Recombinant HIV-1 A3/CRF02_AG Compared With Sub-subtype A3

There is a lot to address here, so I am going to break it up into a few posts.

What are 'recombinant viruses'? Are they some new scary development in HIV/AIDS?

There are lots of different 'subtypes' of HIV-1. These subtypes are defined by where a viruses genetic sequence groups in a phylogenetic tree. If you do not know the subtype of a virus, you put it in a phylogenetic tree with, say, the Env gene of lots of viruses you know are Subtype B, Subtype C, etc. The unknown sequence should group with its Subtype in a tree. You can learn all about it in a pdf from the Los Alamos HIV Sequence Database (pdf!).

Different subtypes are more prevalent in different parts of the world-- Like, about 50% of all HIV infections are Subtype C, but less than 1% of infections in the US are C. In the US, we basically only have B.

If someone is infected with two different subtypes, and one cell is infected with both subtypes, because HIV is functionally diploid, two different genomes can be packaged into the same virus. When that virus reverse transcribes, the RT enzyme can hop around between the genomes. That is how we can get recombinant viruses.

From Virus Sexy Time and Recombination: Retrovirus Sex:

So sometimes HIV-1 sexy time leads to subtle polymorphisms:

Sometimes it leads to a gene duplication (or deletion):

And sometimes, if two different kinds of HIV-1 have infected the same cell, a virus can contain two different genomes. When sexy time comes, the resulting baby-virus can be a totally new mixture of its parents:

Well, the subtypes originally formed due to geographic isolation and differential evolution. The world isnt as geographically isolated as it was in 1920. We are living in a global society. It isnt hard for someone from NYC to fly to Paris to Cape Town to Melbourne to Tokyo to Milwaukee. As the viruses 'mix', we are going to be seeing more and more recombinations (we call them Circulating Recombinant Forms, CRFs)

Currently, CRFs make up ~17-18% of HIV infections world wide. In this particular study, 53% (n=78) of the patients were infected with a CRF, 'AG'. And those arent even the recombinants the news is worried about!

53% were AG, 29% were A3 (Subtype A, n=42)-- 19 patients were part AG/A3, and 3 were part A3/AG.

For some reason, they did not analyze the 3 A3/AG patients any further, and they also dropped the patients in their cohort who were infected with a Subtype C (n=2), B (n=1), and a different CRF, CRF06_cpx (n=2).

See? CRFs are freaking everywhere.

It is a side-effect of us traveling a lot and having sex all the time, and HIV-1s replication cycle. If SIV first turned into HIV in modern times, the subtypes would have probably never developed, certainly not to the degree we see (saw) them.

But are recombinant variants more aggressive than their parental strains?

That is the question these researchers set out to investigate. But just to be clear, one of the parent subtypes is a recombinant already (AG). If it was a question of 'if more recombination = more aggressive', then why were the A3/AG variants excluded, while the AG/A3 were included? Indeed, why were the CRF06_cpx patients excluded, as CRF06_cpx is a recombinant between four subtypes (A, G, J, K).

I dont think there is anything inherent in recombinants to make them more aggressive than any other variant. What I would be more concerned about is the spread of antiretroviral resistance.

But whether viruses are evolving to be more aggressive is the next question I am getting...

... to be continued!