Showing papers by "Eva Harris published in 2004"

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Abstract: Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-α/β) and IFN-γ receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-α/β receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-γ receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4 + T, or CD8 + T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-α/β is critical for early immune responses to DEN infection, (ii) IFN-γ-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.

Analysis of recombinant dengue virus polypeptides for dengue diagnosis and evaluation of the humoral immune response

Abstract: Dengue is a serious cause of morbidity and mortality in tropical areas worldwide. We cloned and expressed recombinant polypeptides spanning the entire genome of a Brazilian dengue virus type 2 (DENV-2) strain in contiguous segments to generate antigens for dengue diagnosis and evaluation of the human humoral immune response. When analyzed by Western blot and an enzyme-linked immunosorbent assay (ELISA) using human sera, the most reactive polypeptide (pD2-3(E)) was located in the N-terminal portion of the envelope protein. The sensitivity of an IgG-ELISA using pD2-3(E) versus mouse brain antigen was 100% with convalescent sera and 79% with acute sera, with a specificity of 100%. Sera from patients infected with other DENV serotypes recognized pD2-3(E) equally well, whereas sera positive for yellow fever, rubella, and measles showed little or no reactivity. Using this novel approach, we identified a candidate antigen to facilitate diagnosis of DENV infections and observed a surprising variability in antibody patterns in the clinical response to DENV infections.

Innovative low cost technologies for biomedical research and diagnosis in developing countries

Abstract: The relation between science, technology, and economic development is unquestionable. However, in the poorest countries of the world, this relation is tenuous at best, mainly due to the fact that science and technology typically require a large amount of investment in terms of both capital and higher education. In this article, we document the ingenuity and innovative approaches of our colleagues in developing countries who conduct biomedical research and laboratory diagnosis with limited resources. Not only is what they have achieved laudable, but there is much that the rest of the world can and should learn from these examples. The lack of resources in academic and state laboratories in the developing world produces a creative pressure that forces scientists to invent and reuse as much as possible. The innovations range from substitute equipment, recycling of otherwise disposable materials, and adaptation of cell lines to new temperatures or growth media to simplification of protocols and production of home made kits and reagents.1–6 For example, plastic pipette tips, consumed in large quantities and usually disposed of after one use, can be reused for certain procedures after disinfection and extensive washing. To make the process more efficient and less expensive, an ingenious Bolivian researcher, Nataniel Mamani, created a tip washer from a plastic jar and inner tubing. The tips fit perfectly into the tubing, allowing water to pass through and effectively wash out the bleach and soap used to clean them (fig 1).7 This simple contraption can save a laboratory hundreds of dollars a month. Fig 1 Mamani's pipette tip washer: economic and effective #### Summary points Researchers in the developed world can learn much from the ingenuity and passion of colleagues in developing countries Working in resource poor settings fosters creativity and a mindset for conservation and better management of resources Understanding …