Sequence Analysis of the Human Virome in Febrile and Afebrile Children
Kristine M. Wylie mail,
Kathie A. Mihindukulasuriya,
Erica Sodergren,
George M. Weinstock,
Gregory A. Storch
Abstract
Unexplained fever (UF) is a common problem in children under 3 years old. Although virus infection is suspected to be the cause of most of these fevers, a comprehensive analysis of viruses in samples from children with fever and healthy controls is important for establishing a relationship between viruses and UF. We used unbiased, deep sequencing to analyze 176 nasopharyngeal swabs (NP) and plasma samples from children with UF and afebrile controls, generating an average of 4.6 million sequences per sample. An analysis pipeline was developed to detect viral sequences, which resulted in the identification of sequences from 25 viral genera. These genera included expected pathogens, such as adenoviruses, enteroviruses, and roseoloviruses, plus viruses with unknown pathogenicity. Viruses that were unexpected in NP and plasma samples, such as the astrovirus MLB-2, were also detected. Sequencing allowed identification of virus subtype for some viruses, including roseoloviruses. Highly sensitive PCR assays detected low levels of viruses that were not detected in approximately 5 million sequences, but greater sequencing depth improved sensitivity. On average NP and plasma samples from febrile children contained 1.5- to 5-fold more viral sequences, respectively, than samples from afebrile children. Samples from febrile children contained a broader range of viral genera and contained multiple viral genera more frequently than samples from children without fever. Differences between febrile and afebrile groups were most striking in the plasma samples, where detection of viral sequence may be associated with a disseminated infection. These data indicate that virus infection is associated with UF. Further studies are important in order to establish the range of viral pathogens associated with fever and to understand of the role of viral infection in fever. Ultimately these studies may improve the medical treatment of children with UF by helping avoid antibiotic therapy for children with viral infections.
Citation: Wylie KM, Mihindukulasuriya KA, Sodergren E, Weinstock GM, Storch GA (2012) Sequence Analysis of the Human Virome in Febrile and Afebrile Children. PLoS ONE 7(6): e27735. doi:10.1371/journal.pone.0027735
Editor: Chiyu Zhang, Institut Pasteur of Shanghai, Chinese Academy of Sciences, China
Received: August 12, 2011; Accepted: October 23, 2011; Published: June 13, 2012
Copyright: ? 2012 Wylie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
