title: Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia.
abstract: Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3(422-431) were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3(422-431) and NS5(563-571) in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3(422-431). A large number of patients' T cells also responded to the NS2B(97-106) region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Ramapraba
authors.initials: R
authors.lastname: Appanna
authors.forename: Tan Lian
authors.initials: TL
authors.lastname: Huat
authors.forename: Lucy Lum Chai
authors.initials: LL
authors.lastname: See
authors.forename: Phoay Lay
authors.initials: PL
authors.lastname: Tan
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
authors.forename: Shamala
authors.initials: S
authors.lastname: Devi
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008296:Malaysia; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000276:immunology*; D015678:Viral Structural Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D010455:Peptides; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D007371:Interferon-gamma