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Human Virome Project PI: Greg Storch, MD Co-Investigator: Michele Estabrook, MD Coordinators: Avrumi Smason and Sherry Lassa-Claxton

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Human Virome Project PI: Greg Storch, MD Co-Investigator: Michele Estabrook, MD Coordinators: Avrumi Smason and Sherry Lassa-Claxton Human Virome Project PI: Greg Storch, MD Co-Investigator: Michele Estabrook, MD Coordinators: Avrumi Smason and Sherry Lassa-Claxton Goal The goal of this project is to describe the human virome in normal and immunocompromised children and to assess the relationship between alterations in the virome and acute febrile illnesses in childhood. Definition of the human virome: The concept of a human virome is new and presently lacks an accepted definition. For the purposes of this proposal, the human virome is defined as the total collection of viruses that infect humans. An individual’s virome is defined as the total collection of viruses infecting the individual at a single point in time. The virome includes viruses causing acute (symptomatic or asymptomatic) infection, persistent infection, and latent infection. However, as used here, it does not include viral sequences that are present in the human germ line for which there is no evidence for complete virus replication at any stage of the virus life cycle. Overview of the proposed project: This project will begin the process of defining the human virome in young children. High throughput sequencing directed at detection of known and unknown viruses will be performed on samples of blood, respiratory and gastrointestinal secretions from cohorts of a) well children, b) otherwise well children being evaluated in an emergency room for fever without an evident source, c) immunocompromised children who are clinically stable, and d) immunocompromised children who are experiencing a febrile illness without an evident cause, and e) hematopoietic stem cell (HSC) and solid organ transplant patients before and after transplant. When possible, samples will also be obtained from the transplant donor. The children being evaluated for acute febrile illnesses will have additional samples obtained at follow-up visits 1 month and 6 months after the febrile illness. Based on our preliminary studies, we anticipate finding a large number of viruses. The significance of the viruses detected will be investigated using a series of approaches. In addition, also based on our preliminary studies, we also anticipate finding previously unrecognized viruses. We will characterize these viruses by sequencing their whole genomes and investigating their prevalence in the cohorts of subjects enrolled in this study. NP swabs Stool Collection Blood Samples Febrile children study: This is an ongoing study searching for viruses in children with febrile illnesses. Septic infant study: This is a closed to enrollment study for which the PI is Jared Muenzer, MD Pediatric transplant specimen bank: This repository is being established by Dr. Wang and his team to study the prevalence and disease associations of the WU polyomavirus in immunocompromised children. Prospective specimen collection: Subject category No. of subjects No. for high throughput sequencing Well children 200 100 Febrile children 200 100 Immuncompromised children Stable/afebrile 100 20 Febrile 50-100 50 Transplant recipients 100 20 Transplant donors 20 14 Well children Otherwise healthy Immunocompromised children with fever children and New Transplants •SLCH ED for non-infectious •Immunocompromised children conditions and from •SLCH Emergency who are not ill will be recruited to children having elective provide baseline samples. Department for fever surgery at SLCH or an •a) children who have had HSC or affiliated facility who will solid organ transplants undergo anesthesia for •b) children with HIV/AIDS followed elective surgery for a non- in the HIV clinic acute condition •c) children with congenital Participants with fever and immunodeficiencies or diseases requiring prolonged treatment new transplants will be with high doses of followed at one and six immunosuppressive medications months who are followed in the immunology and rheumatology clinics This Human Virome Study is part of the large project organized by the NIH called the Human Microbiome Project, the aim of which is to define the microbial flora that are associated with humans, and to investigate the effects of that flora on health and disease. .
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