Tracking evolution of ‘mouse HIV’ virus back to dinosaurs

06 March 2014

HIV virus illustration

Image: HIV virus illustration

Researchers at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) have made advances in understanding the evolution of retroviruses - the family of viruses that includes HIV, which causes humans AIDS. 

Dr Jonathan Stoye's team at NIMR first cloned and characterised a mouse gene that confers resistance to retrovirus infection in 1996. Since then, they have continued to study the evolution of the gene, called Fv1. Now, the group has developed a model for the evolution of resistance to retrovirus infection, providing insights into the HIV pandemic currently affecting humans. 

The work involved studying so-called endogenous retroviruses - which are remnants of ancient retrovirus infection that have accumulated in our DNA but can no longer replicate. 

Dr Stoye explained: "Endogenous retroviruses are 'molecular fossils' that have made their homes in the DNA of all mammals. These  tell us that we have been confronted, in a series of waves, by new infectious retroviruses for a period going back as least as far as the dinosaur. HIV-1 is just one of the most recent examples.  

"During this time, a number of mechanisms to limit the spread of these viruses have arisen within the hosts, such as genes that provide resistance to infection. When new infections occur, these genes can continue to evolve, providing a way to combat new retroviruses." 

In their most recent work, the scientists tracked the evolution of the mouse Fv1 gene, which prevents a mouse retrovirus called MLV from replicating. They found that, over the last 4 million years, several changes in the sequence of Fv1 caused amino acid changes in the protein coded for by the gene. Proteins are made from strings of amino acids - the sequence of these affects the protein's structure and function. 

The research findings suggest that, on at least four separate occasions, these amino acid changes were caused by selection pressure from the appearance of new viruses. 

Dr Stoye explained: "In the same way that humans are currently exposed to a new pandemic infection caused by the HIV-1 virus jumping from another species, we believe that over time, mice have been infected by a series of new retroviruses.  Survival may depend on the development of resistance to each of these.  

He added: "This work provides an interesting model system for studying the evolution of resistance to infection by different kinds of retrovirus."

The paper, Evolution of the retroviral restriction gene Fv1: inhibition of non-MLV retroviruses, is published in PLOS Pathogens.

  • Studying the evolution of retroviruses has given scientists insights into the current human pandemic caused by HIV, a member of the retrovirus family of viruses. 
  • The team, from the Medical Research Council's National Institute for Medical Research, studied endogenous retroviruses - ancient retroviruses that have accumulated in our genome during evolution but can no longer replicate. 
  • A study published last year showed that endogenous retroviruses were widespread in the genomes of 38 mammals including humans. Astonishingly, some of the viruses could be traced back to common ancestors that existed up to 100 million years ago. Although they have lost the ability to replicate, many endogenous retroviruses are so widely distributed throughout the mammal genomes studied that they could be iindicative of multiple previous disease epidemics.