The family Retroviridae comprises a large number of enveloped, spherical to pleomorphic viruses with a linear, positive-sense, single-stranded RNA genome of 7 – 11 kb and a size of 80 – 100 nm. These viruses are furthermore classified into 2 subfamilies and 7 genera.
Their common characteristic which is represented in the name of the family is the enzyme reverse transcriptase. It enables the virus to reverse the flow of the genetic information from RNA to DNA. During the replication cycle, the ssRNA(+) is copied into dsDNA which is integrated into the cell’s genome (=provirus). Retroviruses are known to cause a wide range of diseases in both humans and many animal species, especially immunodeficiencies and tumours.
We are currently involved in sequencing projects considering the Human immunodeficiency virus (HIV), the causative agent of the ongoing acquired immune deficiency syndrome (AIDS) pandemic.
In collaboration with Myra McClure & Jonathan Weber (Imperial College London), we are involved in the SPARTAC study (Short Pulse Anti Retroviral Therapy at HIV Seroconversion) funded by the Wellcome Trust. It is a randomised-controlled trial comparing three different strategies of intervention in patients recently infected with HIV, i.e. (i) Long Course combination Anti-Retroviral Therapy (LCART) for 48 weeks, (ii) Short Course combination Anti-Retroviral Therapy (SCART) for 12 weeks and (iii) No Anti-Retroviral Therapy. The main objective is to determine whether treatment at primary infection for a limited duration delays damage to the immune system and prolongs time to initiation of long-term anti-HIV therapy. The CD4 cell counts as well as disease progression and the development of AIDS events will be monitored.
At the Sanger Institute, we are performing deep sequencing of the highly variable V3 region of the envelope gene using Roche/454 technology. The obtained very deep coverage enables us to identify minor variants. We will compare the sequence diversity before and after treatment within each patient and between groups to investigate whether the intensity of selection has an impact on the viral genetic diversity.
More information about the study can be found here
We are also working with Deenan Pillay (University College London) to generate whole genome sequences of diverse HIV strains from the UK isolated from the 1980’s until today. Phylogenetic analysis will be conducted to estimate evolution rates and to measure the impact of selective pressures (e.g. highly active antiretroviral therapy, humane restriction factors) on the unprecedented genetic diversity of this virus.
Published Genome Data
The reference sequence for the Human immunodeficiency virus 1 can be found here
This project is ongoing and data for this organism will be made available in due course.
Data Use Statement
This sequencing centre plans on publishing the completed and annotated sequences in a peer-reviewed journal as soon as possible. Permission of the principal investigator should be obtained before publishing analyses of the sequence/open reading frames/genes on a chromosome or genome scale. See our data sharing policy.
Please address all sequencing enquiries to: firstname.lastname@example.org