These data indicate a potential clinical use of Ca-SP containing Spirulina species extract for the prophylactic treatment of herpes labialis and suggest possible activity of Ca-SP against infections caused by other herpesviruses.

How innate and adaptive immune responses work in concert to resolve influenza disease is yet to be fully investigated in one single study. Here, we utilize longitudinal samples from patients hospitalized with acute influenza to understand these immune responses. We report the dynamics of 18 important immune parameters, related to clinical, genetic and virological factors, in influenza patients across different severity levels. Influenza disease correlates with increases in IL-6/IL-8/MIP-1α/β cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells correlates with peak antibody-secreting cells and influenza heamaglutinin-specific memory B-cell numbers, which phenotypically differs from vaccination-induced B-cell responses. Numbers of influenza-specific CD8+ or CD4+ T cells increase early in disease and retain an activated phenotype during patient recovery. We report the characterisation of immune cellular networks underlying recovery from influenza infection which are highly relevant to other infectious diseases.

Adenovirus often causes respiratory infection in immunocompromised patients, but relevant attachment receptors have largely not been defined. We show that the antiviral protein bovine lactoferrin enhances infection of monocyte-derived dendritic cells (MDDC) by adenovirus species C serotype 2 (2C) isolates. Under the same conditions infection of MDDC by human cytomegalovirus was reduced. Adenoviral infection was prominently enhanced by bovine but not human lactoferrin, and was not prominently enhanced using blood monocyte-derived macrophages, suggesting that the relevant receptor is expressed on MDDC. Infection of MDDC in the presence of bovine lactoferrin was blocked by mannan, and an antibody to CD209/DC-SIGN but not isotype control or CD46 antibodies. Lastly, U937 macrophages ectopically expressing CD209/DC-SIGN, but not parental U937 cells, were efficiently infected by adenovirus 2C in the presence of bovine lactoferrin. These results may provide a tool, given the high efficiency of infection, to dissect responses by myeloid cells to clinical adenovirus isolates.Adenoviruses are common viral pathogens, particularly following allogeneic haematopoetic stem-cell transfer, with potentially fatal consequences (Feuchtinger et al., 2007). There is currently no universally accepted therapy. Adenovirus species C serotype 2 (2C) often causes respiratory infection, but the relevant attachment receptors on cells in the lung have largely not been defined.Cells that mediate innate immune responses to adenoviruses and adenoviral vectors include alveolar epithelial cells, macrophages, plasmocytoid and conventional dendritic cells (DC) (Muruve, 2004; Wu et al., 2010;Zhu et al., 2007). While great progress has been made in recent years in understanding the innate immune response to adenovirus and adenoviral vectors, particularly through intracellular inflammasomes and retinoic acid-inducible gene I-like receptors (Chiu et al., 2009;Di Paolo et al., 2009;Muruve et al., 2008;Zaiss et al., 2009), little is known about attachment receptors on myeloid cells. A variety of mechanisms and receptors may be used for adenoviral infection (Arnberg, 2009). The majority of adenoviruses initially engage an attachment receptor, following which RGD motifs within the penton base contact integrins that mediate viral internalization. The commonly used attachment receptor CAR (coxsackie virus and adenovirus receptor) is poorly accessible in the lung, and has been suggested to be not relevant for infection in vivo (Arnberg, 2009). CD46 is a second well characterized receptor that mediates efficient infection of many cell types including myeloid cells, but only functions for particular species B adenoviruses (Gaggar et al., 2003). Bridging molecules such as dipalmitoyl phosphatidylcholine, a major component of pulmonary surfactant, or lactoferrin, an antiviral protein abundantly expressed in the lung, mediate infection by species C adenoviruses (Balakireva et al., 2003;Johansson et al., 2007;Adams et al., 2009). Although the identity of dipalmitoyl ...

Infection with adenovirus is a major cause of infectious mortality in children following hematopoietic stem-cell transplantation. While adoptive transfer of epitope-specific T cells is a particularly effective therapeutic approach, there are few suitable adenoviral peptide epitopes described to date. Here, we describe the adenoviral peptide epitope FRKDVNMVL from hexon protein, and its variant FRKDVNMIL, that is restricted by human leukocyte antigen (HLA)-C*0702. Since HLA-C*0702 can be recognized by both T cells and natural killer (NK) cells, we characterized responses by both cell types. T cells specific for FRKDVNMVL were detected in peripheral blood mononuclear cells expanded from eight of ten healthy HLA-typed donors by peptide-HLA multimer staining, and could also be detected by cultured interferon γ ELISpot assays. Surprisingly, HLA-C*0702 was not downregulated during infection, in contrast to the marked downregulation of HLA-A*0201, suggesting that adenovirus cannot evade T cell responses to HLA-C*0702-restricted peptide epitopes. By contrast, NK responses were inhibited following adenoviral peptide presentation. Notably, presentation of the FRKDVNMVL peptide enhanced binding of HLA-C*0702 to the inhibitory receptor KIR2DL3 and decreased NK cytotoxic responses, suggesting that adenoviruses may use this peptide to evade NK responses. Given the immunodominance of FRKDVNMVL-specific T cell responses, apparent lack of HLA-C*0702 downregulation during infection, and the high frequency of this allotype, this peptide epitope may be particularly useful for adoptive T cell transfer therapy of adenovirus infection.