Casto, A. M. | bioRxiv Science

bioRxiv2018

The impact of interspecies recombination on human herpes simplex virus evolution and host immune recognition

Among the most ubiquitous of human pathogens, HSV-1 and HSV-2 are distinct viral species that diverged about six million years ago. At least four ancient HSV-1 x HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and non-recombinants at each locus circulating today. Though interspecies recombination has occurred in the past, its importance in HSV evolution remains incompletely defined. Using 255 newly-sequenced and 219 existing HSV genome sequences, we comprehensively assessed interspecies recombination in HSV. The novel recombinants we identify demonstrate that the sizes and locations of interspecies recombination events in HSV-2 are more variable than previously appreciated. One novel recombinant arose in its current host, showing for the first time that interspecies recombination occurs in contemporary HSV populations. We also demonstrate that interspecies recombination affects T-cell recognition of HSV. Our findings indicate that interspecies recombination can significantly influence genetic variation in and host immunologic response to HSV-2.

genomics↗

bioRxiv2018

Prospective real-time metagenomic sequencing during norovirus outbreak reveals discrete transmission clusters

BackgroundNorovirus outbreaks in hospital settings are a common challenge for infection prevention teams. Given the high burden of norovirus in most communities, it can be difficult to distinguish between on-going in-hospital transmission of virus and new introductions from the community and challenging to understand the long-term impacts of outbreak-associated viruses within medical systems using traditional epidemiological approaches alone.\n\nMethodsReal-time metagenomic sequencing during an on-going norovirus outbreak associated with a retrospective cohort study.\n\nResultsWe describe a hospital-associated norovirus outbreak that affected 13 patients over a 27-day period in a large tertiary pediatric hospital and was chronologically associated with a spike in self-reported gastrointestinal symptoms among staff. Real-time metagenomic next-generation sequencing (mNGS) of norovirus genomes demonstrated that 10 chronologically overlapping hospital-acquired norovirus cases were partitioned into three discrete transmission clusters. Sequencing data also revealed close genetic relationships between some hospital-acquired and some community-acquired cases. Finally, this data was used to demonstrate chronic viral shedding by an immunocompromised hospital-acquired case patient. Analysis of serial samples from this patient provided novel insights into the evolution of norovirus within an immunocompromised host.\n\nConclusionsThis study documents one of the first applications of real-time mNGS during a hospital-associated viral outbreak. Given its demonstrated ability to detect transmission patterns within outbreaks and elucidate the long-term impacts of outbreak-associated viral strains on patients and medical systems, mNGS constitutes a powerful resource to help infection control teams understand, prevent, and respond to viral outbreaks.\n\nSummary StatementReal-time metagenomic sequencing performed during a hospital-associated norovirus outbreak identified genetically-distinct, chronologically-overlapping case clusters. After the epidemiologically-defined outbreak had ceased, on-going transmission and shedding of outbreak-associated virus was also detected. These findings illustrate the value of genomics as a tool for infection control.

genomics↗