TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers.

SOLUTION: Protein Microarrays and Biomarkers of Infectious Disease

PROBLEM: Porcine blood mononuclear cells (PBMC) were shown to produce interferon-a (IFNa) following incubation with cells infected by a coronavirus, transmissible gastroenteritis virus. Monoclonal antibodies (mAb) with specificities for leukocyte subsets and major histocompatibility complex (MHC) antigens were used to characterize IFNa producer cells. The production of IFNa was found to be a function of non-phagocytic, non-adherent, non-T, non-B, CD4 + (and to a lesser extent CD8 +) MHC-class-II-positive ceils. Furthermore, addition of anti-MHC (class II) mAb during PBMC incubation with virus-infected cells reduced IFN yields, suggesting that masking of these surface antigens alters PBMC responsiveness to IFN induction.

SOLUTION: CHARACTERIZATION OF BLOOD MONONUCLEAR CELLS PRODUC- ING IFNa FOLLOWING INDUCTION BY CORONAVIRUS-INFECTED CELLS (PORCINE TRANSMISSIBLE GASTROENTERITIS VIRUS)

PROBLEM: Respiratory Syncytial Virus (RSV) is a highly pathogenic member of the Paramyxoviridae that causes severe respiratory tract infections. Reports in the literature have indicated that to infect cells the incoming viruses either fuse their envelope directly with the plasma membrane or exploit clathrin-mediated endocytosis. To study the entry process in human tissue culture cells (HeLa, A549), we used fluorescence microscopy and developed quantitative, FACS-based assays to follow virus binding to cells, endocytosis, intracellular trafficking, membrane fusion, and infection. A variety of perturbants were employed to characterize the cellular processes involved. We found that immediately after binding to cells RSV activated a signaling cascade involving the EGF receptor, Cdc42, PAK1, and downstream effectors. This led to a series of dramatic actin rearrangements; the cells rounded up, plasma membrane blebs were formed, and there was a significant increase in fluid uptake. If these effects were inhibited using compounds targeting Na + /H + exchangers, myosin II, PAK1, and other factors, no infection was observed. The RSV was rapidly and efficiently internalized by an actin-dependent process that had all hallmarks of macropinocytosis. Rather than fusing with the plasma membrane, the viruses thus entered Rab5-positive, fluidfilled macropinosomes, and fused with the membranes of these on the average 50 min after internalization. Rab5 was required for infection. To find an explanation for the endocytosis requirement, which is unusual among paramyxoviruses, we analyzed the fusion protein, F, and could show that, although already cleaved by a furin family protease once, it underwent a second, critical proteolytic cleavage after internalization. This cleavage by a furin-like protease removed a small peptide from the F1 subunits, and made the virus infectious.

SOLUTION:
Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein