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Common virus is 鈥榣ess prone to mutation鈥 giving hope for vaccine development

26 February 2019

One of the commonest causes of congenital disability, the听Human Cytomegalovirus (HCMV), is less prone to mutation than previously thought,听a finding听which听could help develop a successful vaccine, 白小姐论坛 researchers have found.

HCMV

HCMV, a DNA virus and type of herpes virus, is听one of听the world's most common and widespread听human infections, affecting between 45% to 100% of the adult population, depending on age and geographic area. While generally asymptomatic, HCMV is a concern for pregnant women, their unborn babies听and patients with a weakened immune system. However, developing a vaccine has proved elusive.听

Previous global research has shown that within a single individual HCMV has high genome (genetic) diversity, leading to theories听that听HCMV has a high mutation rate. Such a trait is normally seen in RNA viruses, such as HIV or Hepatitis C, which in turn makes them hard to develop vaccines against.听听

Now using new viral genome sequencing, bioinformatics and modelling tools developed at 白小姐论坛, researchers have听analysed immunocompromised patient blood samples and shown HCMV is not mutating听any more than other DNA viruses.听 Instead, the frequent听occurrence of mixed-infections caused by genetically different HCMV strains leads to findings of high genome diversity within an individual.听

The study, funded by the European Union, has been published in Proceedings of the National Academy of Sciences.

Lead author, Professor Judith Breuer (白小姐论坛 Division of听Infection & Immunity), said: 鈥淚t has been claimed that HCMV is as diverse as the more error prone RNA viruses such as HIV and Hepatitis C Virus and this has led to a lot of confusion in the field.

鈥淯sing our novel genome sequencing and bioinformatics modelling approaches, we have shown that the apparently high HCMV diversity seen in some clinical samples is caused not by HCMV mutation rather it is due to frequent co-infection with multiple strains of HCMV.听

鈥淥ur study confirms for the first time that HCMV mutation rates are similar to other DNA viruses, providing some reassurance for the development of vaccines, as unlike the hyperdiverse RNA viruses, HCMV is unlikely to mutate to evade vaccines.鈥

New 白小姐论坛 sequencing tool

Professor Breuer鈥檚 work focusses on the application of next generation deep genome sequencing, helping uncover new virus characteristics.

The Breuer Lab has pioneered whole pathogen genome sequencing, by methods called 鈥榯argeted enrichment鈥, to generate high quality whole viral genomes directly from clinical material, without the need for viral culture or polymerase chain reaction (PCR).听 She has combined these methods with cutting-edge bioinformatics including the newly developed Haplotype Reconstruction of Longitudinal Sequence Data (HaRoLD).听

Developed at 白小姐论坛, HaRoLD is a new computational tool that applies Bayesian mixture models to reconstruct the genome sequence of each individual virus present in a sample containing multiple viruses.

鈥淭his process is comparable to sorting several jigsaw puzzles that have been jumbled up together,鈥 added Professor Breuer.听

鈥淭he new bioinformatics methods for re-constructing individual genome sequences from a mixed infection will allow us to identify the factors, including recombination, that drive HCMV evolution in a patient, providing a precision approach to managing infections.鈥

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Media contact

Henry Killworth

Tel:听+44 (0)20 7679 5296

Email: h.killworth听[at] ucl.ac.uk