T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children.

Background: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, >90% of the population was DENV-naïve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection.

Methods: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers.

Conserved cysteine residues within the attachment G glycoprotein of respiratory syncytial virus play a critical role in the enhancement of cytotoxic T-lymphocyte responses.

The cytotoxic T-lymphocyte (CTL) response plays an important role in the control of respiratory syncytial virus (RSV) replication and the establishment of a Th1-CD4+ T cell response against the virus. Despite lacking Major Histocompatibility Complex I (MHC I)-restricted epitopes, the attachment G glycoprotein of RSV enhances CTL activity toward other RSV antigens, and this effect depends on its conserved central region. Here, we report that RSV-G can also improve CTL activity toward antigens from unrelated pathogens such as influenza, and that a mutant form of RSV-G lacking four conserved cysteine residues at positions 173, 176, 182, and 186 fails to enhance CTL responses.

Breastfeeding is associated with the production of type I interferon in infants infected with influenza virus.

Background: Breast milk-mediated protection against respiratory viruses is well established. However, protective mechanisms are unclear. Type I interferons (IFN) mediate host defence against respiratory viruses, particularly influenza virus.

Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina.

Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children.

Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children.

Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure.

Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease.

Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. The transcription factor Nrf2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene induction.

Objectives: The current study was designed to determine the role of Nrf2-mediated cytoprotective mechanisms in murine airway RSV disease.

Differential gender response to respiratory infections and to the protective effect of breast milk in preterm infants.

Objective: The protective role of breastfeeding against severe acute lung disease in infants is well established, but its mechanism is unclear. Most hypotheses assume that breastfeeding confers similar passive protection to every infant; however, a few observations have suggested that the benefits of breast milk against severe lung disease may differ according to gender. The objective of this study was to determine whether the effect of breastfeeding on susceptibility to severe acute lung disease among infants at high risk is different for girls and boys.

Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus, or influenza virus in infants.

Objectives: We characterized the T helper cytokine profiles in the respiratory tract of infants infected with influenza virus, human metapneumovirus, and respiratory syncytial virus to examine whether these agents elicit similar cytokine responses and whether T helper type 2 polarization is associated with wheezing and severe disease.

Methods: A prospective study of infants who were seeking medical help for acute upper and/or lower respiratory tract infection symptoms for the first time and were found to be infected with influenza, human metapneumovirus, or respiratory syncytial virus was performed. Respiratory viruses were detected in nasal secretions with reverse transcriptase-polymerase chain reaction assays.

Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus.

Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2(d)-restricted CTL epitope in the M2-2 protein has been described. In this study, we screened the hMPV F, G, N, M, M2-1, and M2-2 proteins using three independent algorithms to predict H-2(d) CTL epitopes in BALB/c mice.

C5 modulates airway hyperreactivity and pulmonary eosinophilia during enhanced respiratory syncytial virus disease by decreasing C3a receptor expression.

Enhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes.

Characterization of human metapneumovirus infection of myeloid dendritic cells.

Recent in vivo studies suggest that hMPV is a poor inducer of inflammatory cytokines and that clinical symptoms may not be related to immune-mediated pathogenesis as it has been proposed for respiratory syncytial virus (RSV) and human parainfluenza 3 (HPF3). Dendritic cells (DCs) are specialized antigen presenting cells, and very effective at inducing specific CTLs after encountering invading viruses. Interactions of hMPV with DCs have not been characterized.

The cysteine-rich region and secreted form of the attachment G glycoprotein of respiratory syncytial virus enhance the cytotoxic T-lymphocyte response despite lacking major histocompatibility complex class I-restricted epitopes.

The cytotoxic T-lymphocyte (CTL) response is important for the control of viral replication during respiratory syncytial virus (RSV) infection. The attachment glycoprotein (G) of RSV does not encode major histocompatibility complex class I-restricted epitopes in BALB/c mice (H-2(d)). Furthermore, studies to date have described an absence of significant CTL activity directed against this protein in humans.

The impact of infection with human metapneumovirus and other respiratory viruses in young infants and children at high risk for severe pulmonary disease.

We conducted a prospective, observational study to characterize the clinical manifestations of respiratory infections caused by human metapneumovirus (hMPV) and other viruses in 194 premature infants and young children with chronic lung disease or congenital heart disease in Buenos Aires. Children had 567 episodes of respiratory illness and were monitored until they were 2 years old or until the completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of moderate or greater severity.

The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin.

The attachment protein (glycoprotein) of respiratory syncytial virus (RSV) has long been associated with disease potentiation and respiratory symptoms. The glycoprotein has a conserved cysteine-rich region (GCRR) whose function is unknown and which is not necessary for efficient viral replication. In this report, we show that the GCRR is a powerful inhibitor of the innate immune response against RSV, and that early secretion of glycoprotein is critical to modulate inflammation after RSV infection.