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Dengue virus (DENV) is transmitted by infectious mosquitoes during blood-feeding via saliva containing biologically-active proteins. Here, we examined the effect of varying DENV infection modality in rhesus macaques in order to improve the DENV nonhuman primate (NHP) challenge model. NHPs were exposed to DENV-1 via subcutaneous or intradermal inoculation of virus only, intradermal inoculation of virus and salivary gland extract, or infectious mosquito feeding. The infectious mosquito feeding group exhibited delayed onset of viremia, greater viral loads, and altered clinical and immune responses compared to other groups. After 15 months, NHPs in the subcutaneous and infectious mosquito feeding groups were re-exposed to either DENV-1 or DENV-2. Viral replication and neutralizing antibody following homologous challenge were suggestive of sterilizing immunity, whereas heterologous challenge resulted in productive, yet reduced, DENV-2 replication and boosted neutralizing antibody. These results show that a more transmission-relevant exposure modality resulted in viral replication closer to that observed in humans., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Yannick Vanloubbeeck, Clarisse Lorin, Marie-Pierre Malice, David Vaughn, and Lucile Warter are employees of the GSK group of companies.

A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in California. Postmortem examination identified a pale, enlarged liver, mildly increased fluid in the lungs, and red foci in the spleen. Histologic examination revealed marked hepatic necrosis with syncytia, splenic necrosis, and interstitial pneumonia with eosinophilic intranuclear inclusions within hepatocytes and in unidentified cells of the lung. Transmission electron microscopy identified virions consistent with a herpesvirus in the nucleus and cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus in the subfamily Alphaherpesvirinae., (© 2016 The Author(s).)

Inflammation is a critical component of asthma. Drugs that control asthma generally reduce the degree of airway inflammation. There is theoretical controversy surrounding the effects of beta(2)-agonists on airway inflammation, with some studies suggesting an anti-inflammatory effect, and others predicting a proinflammatory influence. We conducted a double-blind, placebo-controlled, crossover study of the effect of the long-acting beta(2)-agonist salmeterol on airway inflammation induced by segmental allergen challenge (SAC). We studied 13 allergic asthmatics controlled with as needed inhaled short-acting beta(2)-agonists alone, and used bronchoalveolar lavage 5 min and 48 h after SAC to assess airway inflammation, and the effects of salmeterol on this process. Salmeterol therapy improved FEV(1), but had no significant effect on the immediate or late cellular response to SAC. One measure of superoxide production was reduced, and interleukin-4 (IL-4) was reduced in baseline samples, but other indices of airway inflammation were unchanged by salmeterol therapy. We conclude that salmeterol therapy alone does not meaningfully reduce airway inflammation induced by SAC, but equally importantly, does not result in amplified inflammation.

Respiratory syncytial virus (RSV) and adenovirus (Advs) serotype 3 (Adv3) and 7h (Adv7h) are associated with mild to severe respiratory infection and are indistinguishable during the acute phases of the illnesses. However, outcome and long-term prognosis are different with both infections. RSV infection is associated with later development of asthma, and Adv, mainly Adv7h, with severe lung damage, bronchiectasis, and hyperlucent lung. We hypothesized that this difference could be partly due to different immune responses induced by these viruses. To test this hypothesis we quantified TCD4+, TCD8+, and BCD19+ expressing the interleukin-2 receptor-alpha chain (CD25) and interferon-gamma (IFN-gamma), interleukin (IL)-10, and IL-4 in the supernatant of peripheral blood mononuclear cells (PBMC) from school children infected in vitro with and without RSV, Adv7h, and Adv3 and after phytohemagglutinin (PHA) stimulation in the presence or absence of these viruses at a multiplicity of infection (MOI) of 1. PBMC from every child produced more IL-10 (p

Viral infections have been associated with cellular immune responses and production of Th-1 cytokines. Respiratory syncytial virus (RSV), however, induces virus-specific IgE, which might be a consequence of a Th-2-like activation. To test this hypothesis we quantified interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the supernatant of peripheral blood mononuclear cells cultured for 24 and 48 h in the presence or absence of phytohemaglutinin and pokeweed mitogen and the lymphocyte phenotypes to analyze subsets and their activation markers, from 15 hospitalized infants during an acute lower respiratory infection caused by RSV and 17 healthy control infants from 1 to 15 mo of age. Compared with the control infants, those infected with RSV had an increase in the number of B-cells (p < 0.02) and decreases in both CD8+ T-cells (p < 0.01) and activated CD8+/CD25+ suppressor/ cytotoxic T-cells (p < 0.007). In RSV-infected infants, IFN-gamma production was subtotally suppressed, whereas IL-4 production was decreased to a lesser degree, giving significantly (p < 0.001) increased IL-4/IFN-gamma ratio compared with that in the control infants. These findings suggest a predominant Th-z-like response in RSV-infected infants, which could explain some aspects of the immunopathogenesis of RSV infection and the RSV-specific and nonspecific IgE antibody responses observed.