SummaryKiller immunoglobulin‐like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR–HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self‐limited viral infections. During our investigation of CD8+ T cell responses to a conserved HLA‐B57‐restricted epitope derived from dengue virus (DENV) non‐structural protein‐1 (NS1), we observed substantial binding of the tetrameric complex to non‐T/non‐B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long‐standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56dim NK cells, which are known to express KIRs. Using depletion studies and KIR‐transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA‐B57+ subjects with acute DENV infection revealed marked activation of NS1 tetramer‐binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR–HLA interactions in the modulation of disease outcomes.

e9015th ICID Abstracts / International Journal of Infectious Diseases 16S (2012) e2-e157 mild flu-like symptoms to bronchiolitis and severe pneumonia, and predisposes to the development of asthma. Preterm birth and pre-existing respiratory tract disorders increase risk of developing severe RSV infection. There is conflicting evidence about whether severe RSV disease is correlated to RSV genotype. Molecular epidemiological data from tropical Asia is relatively lacking. This study aims to identify the potential risk factors of severe RSV infection by analysis of clinical data and RSV genotypes in Malaysia.Methods: The medical records of 138 RSV cases were analysed for demographic and clinical data, including age, gender, ethnicity, prematurity, co-morbidity, and source of infection. Severe RSV infection was defined in patients who died, or required ventilation, intensive care, or inotropes. The hypervariable region of the G gene was sequenced for 91 RSV samples from 1989-2009, for genotype identification and phylogenetic analysis. Demographic factors, clinical factors and genotype were entered into logistic regression analysis as predictors of severe RSV disease. A p-value of <0.05 was considered significant.Results: The mean age of the study population was 1.4 years, with a majority (62.3%) aged <1 year. Multivariate analysis showed three independent predictors of severe RSV: male gender (odds ratio 4.25; 95% confidence intervals 1.14-15.85), underlying comorbidity or prematurity (OR 7.11;, and nosocomial infection (OR 4.71;). Genotype was not associated with severity. Of the 91 RSV samples sequenced, 66 (72.5%) were in subgroup A and 25 (27.5%) were in subgroup B. The most commonly detected genotypes were GA2 (52.8%, n=48), GB13 (20.9%, n=19), and GA5 (13.2%, n=12). Nucleotide and amino acid similarity between subgroups were 49.9% and 27.0%. RSV A was detected every year, but RSV B only circulated for 2-3 years before being undetected for 1-2 years.Conclusion: Male gender, underlying co-morbidity or prematurity, and nosocomial infection increases the risk of developing severe RSV infection. RSV A was seen every year, while RSV B circulated in 4-5 year cycles.

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