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Journal of Virology, April 2007, p. 3904-3912, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01887-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Rotavirus Infection Alters Peripheral T-Cell Homeostasis in Children with Acute Diarrhea{triangledown}

Yuhuan Wang,1 Penelope H. Dennehy,2 Harry L. Keyserling,3 Kevin Tang,4 Jon R. Gentsch,1 Roger I. Glass,1,5 and Baoming Jiang1*

Division of Viral Diseases,1 Scientific Resources Program, Centers for Disease Control and Prevention,4 Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia,3 Division of Pediatric Infectious Diseases, Rhode Island Hospital, Providence, Rhode Island,2 Fogarty International Center, National Institutes of Health, Bethesda, Maryland5

Received 30 August 2006/ Accepted 22 January 2007

The patterns of gene expression and the phenotypes of lymphocytes in peripheral blood mononuclear cells (PBMC) from children with diarrhea caused by rotavirus and healthy children were compared by using DNA microarray, quantitative PCR, and flow cytometry. We observed increased expression of a number of genes encoding proinflammatory cytokines and interferon or interferon-stimulated proteins and demonstrated activation of some genes involved in the differentiation, maturation, activation, and survival of B lymphocytes in PBMC of patients with rotavirus infection. In contrast, we observed a consistent pattern of lower mRNA levels for an array of genes involved in the various stages of T-cell development and demonstrated a reduction in total lymphocyte populations and in the proportions of CD4 and CD8 T lymphocytes from PBMC of patients. This decreased frequency of T lymphocytes was transient, since the proportions of T lymphocytes recovered to almost normal levels in convalescent-phase PBMC from most patients. Finally, rotavirus infection induced the activation and expression of the early activation markers CD83 and CD69 on a fraction of CD19 B cells and the remaining CD4 and CD8 T lymphocytes in acute-phase PBMC of patients; the expression of CD83 continued to be elevated and was predominantly exhibited on CD4 T lymphocytes in convalescent-phase PBMC. On the basis of these findings at the molecular, phenotypic, and physiologic levels in acute-phase PBMC, we conclude that rotavirus infection induces robust proinflammatory and antiviral responses and B-cell activation but alters peripheral T-cell homeostasis in children.

* Corresponding author. Present address: Gastroenteritis and Respiratory Viruses Branch, MS G04, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road, Atlanta, GA 30333. Phone: (404) 639-2861. Fax: (404) 639-3645. E-mail: bjiang{at}cdc.gov

{triangledown} Published ahead of print on 31 January 2007.

Journal of Virology, April 2007, p. 3904-3912, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01887-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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