In an article published in Nature Microbiology today, Dr. Paul DW Kirk from MRC Biostatistics Unit, together with Drs. Maxime Huvet, Anat Melamed, Goedele N Maertens and Prof. Charles RM Bangham from Imperial College London, present research into how retroviruses function.
Retroviruses, such as HIV-1 and HTLV-1, are responsible for several human diseases, and a great deal of attention has been given to preventing their transmission through public health strategies. However, there is still much to understand about how retroviruses function and interact with human cells at a molecular level.
Retroviruses can be thought of as little packets of genetic material. When infection occurs, this genetic material gets copied into the DNA of infected cells. A key task is to understand how this integration is targeted — how does the retrovirus “choose” where to insert its genetic material?
Scientists have previously reported that retroviruses target highly symmetric DNA sequence motifs (Figure 1 – right). These motifs are said to be palindromic, because they read the same forwards as their complementary sequences read backwards. For example, using the rules that A and T are complementary, and C and G are complementary, we can see that the sequence x = AAGTGGATATCCACTT has complementary sequence x’ = TTCACCTATAGGAGAA, which is also equal to the reverse of x. This means that x is a palindromic sequence.
The palindromic motifs previously reported to be the targets of retroviruses are actually “averages” that were calculated by combining measurements from large numbers of individual integration sites. In our Nature Microbiology article, we demonstrate that these motifs are not representative averages: in particular, although the “average” sequences are palindromic, the individual integration sites are not. Instead, the individual integration sites seem to fall into two equally sized “positive” and “negative” populations (Figure 2 – left). Using statistical methods to identify these two populations, Dr. Kirk and coworkers have been able to uncover a non-palindromic DNA motif that is shared by several retroviruses.
Work to shed light on the process of retroviral integration is not only of interest to scientists developing new drugs to fight retroviral infection, but also has potential to contribute to the design of safe “gene therapies” that use retroviruses to deliver genetic material into the DNA of an ill patient’s cells, as a way to treat disease.
Read the full article published in Nature Microbiology: http://www.nature.com/articles/nmicrobiol2016212