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Research Article

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

  • Yongsheng Huang,

    Affiliations: Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Statistics, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Aimee K. Zaas,

    Affiliations: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America, Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Arvind Rao,

    Affiliation: Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America

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  • Nicolas Dobigeon,

    Affiliation: IRIT/INP-ENSEEIHT, University of Toulouse, Toulouse, France

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  • Peter J. Woolf,

    Affiliations: Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Timothy Veldman,

    Affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • N. Christine Øien,

    Affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Micah T. McClain,

    Affiliations: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America, Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Jay B. Varkey,

    Affiliation: Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, United States of America

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  • Bradley Nicholson,

    Affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Lawrence Carin,

    Affiliation: Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina, United States of America

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  • Stephen Kingsmore,

    Affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri, United States of America

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  • Christopher W. Woods,

    Affiliations: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America, Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Geoffrey S. Ginsburg mail,

    geoffrey.ginsburg@duke.edu (GSG); hero@eecs.umich.edu (AOH)

    Affiliations: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America, Department of Medicine, Duke University, Durham, North Carolina, United States of America

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  • Alfred O. Hero III mail

    geoffrey.ginsburg@duke.edu (GSG); hero@eecs.umich.edu (AOH)

    Affiliations: Center for Computational Biology and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Statistics, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America, Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Published: August 25, 2011
  • DOI: 10.1371/journal.pgen.1002234

Reader Comments (2)

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Vitamin D may explain some of the findings of this paper

Posted by wbgrant on 26 Sep 2011 at 01:02 GMT

The paper by Huang et al. [1] provides a very interesting set of data on the temporal responses to influenza virus infection in humans. One of the important points was the importance of cytokines in responding to the virus.

Overlooked in the discussion was any mention of the role of vitamin D in affecting risk of influenza infection and adverse effects. There is a growing body of literature that vitamin D reduces the risk of influenza infection and adverse effects from ecological [2] and observational [3] studies and randomized controlled trials [4,5]. There are two mechanisms whereby vitamin D reduces the risk of influenza infection. One is shifting the cytokine balance from T-helper 1 (Th1) towards Th2 cytokines [6]. The other is inducing cathelicidin, which has antimicrobial properties against many types of bacteria as well as viruses with lipid coats [7]. It was found in 2006 that a toll-like receptor response involving vitamin D was involved in responding to Mycobacterium tuberculosis [8], and in 2007 that induction of cathelicidin was involved [9].

An ecological study also found that vitamin D reduces the risk of death after infection by pandemic type A/H1N1 influenza [10].

Thus, the question related to [1] is can any effect of vitamin D be found in the response of the subjects to A/H3N2 infection? One way to address this question is to determine serum 25-hydroxyvitamin D levels from the serum collected at time of infection.


References
1. Huang Y, Zaas AK, Rao A, Dobigeon N, Woolf PJ, et al. (2011) Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection. PLoS Genet 7(8):e1002234.
2. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, et al. (2006) Epidemic influenza and vitamin D. Epidemiol Infect 134:1129-1140.
3. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, et al. (2010) Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One 5:e11088.
4. Aloia JF, Li-Ng M. (2007) Re: epidemic influenza and vitamin D. Epidemiol Infect 135:1095-1096; author reply 1097-1098.
5. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, et al. (2010) Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr 91:1255-1260.
6. Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. (2010) Vitamin D and inflammation. Joint Bone Spine 77(6):552-7.
7. Gombart AF. (2009) The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 4:1151-1165.
8. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, et al. (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770-1773.
9. Liu PT, Stenger S, Tang DH, Modlin RL. (2007) Cutting Edge: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol 179:2060-2063.
10. Grant WB, Giovannucci E. (2009) The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States. Dermato-Endocrinology 1:215-219.

Competing interests declared: I receive funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).