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: We have previously reported that the apathogenic Tula hantavirus induces apoptosis in Vero E6 epithelial cells. To assess the molecular mechanisms behind the induced apoptosis we studied the effects of hantavirus infection on cellular signaling pathways which promote cell survival. We previously also observed that the Tula virus-induced cell death process is augmented by external TNF-. Since TNF- is involved in the pathogenesis of hantavirus-caused hemorrhagic fever with renal syndrome (HFRS) we investigated its effects on HFRS-causing hantavirus-infected cells. We studied both apathogenic (Tula and Topografov) and pathogenic (Puumala and Seoul) hantaviruses for their ability to regulate cellular signaling pathways and observed a direct virusmediated down-regulation of external signal-regulated kinases 1 and 2 (ERK1/2) survival pathway activity, which was dramatically enhanced by TNF-. The fold of ERK1/2 inhibition correlated with viral replication efficiencies, which varied drastically between the hantaviruses studied. We demonstrate that in the presence of a cytokine TNF-, which is increased in HFRS patients, hantaviruses are capable of inactivating proteins that promote cell survival (ERK1/ 2). These results imply that hantavirus-infected epithelial cell barrier functions might be compromised in diseased individuals and could at least partially explain the mechanisms of renal dysfunction and the resulting proteinuria seen in HFRS patients.

SOLUTION: Virology Journal Hantaviruses and TNF-alpha act synergistically to induce ERK1/2 inactivation in Vero E6 cells

PROBLEM: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious 24 disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a 25 high fatality rate. Currently, no specific vaccine or treatment has been approved for this 26 disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-27 displayed antibody library that was constructed from a patient who recovered from SFTS 28 virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope 29 glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in 30 vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 31 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass 32 spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn 33 glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a 34 conformational alteration that is critical for cell membrane fusion between the virus and host 35 cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 36 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 37 247 of 272 reported SFTSV isolates previously reported. Together, these data suggest that 38 Ab10 has potential to be developed into a therapeutic agent that could protect against more 39 than 90% of reported SFTSV isolates. 40 41

SOLUTION: An anti-Gn glycoprotein antibody from a convalescent patient potently 2 inhibits the infection of severe fever with thrombocytopenia syndrome virus

PROBLEM: A substantial proportion of hitherto unexplained respiratory tract illnesses is associated with human metapneumovirus (hMPV) infection. This virus also was found in patients with severe acute respiratory syndrome (SARS). To determine the dynamics and associated lesions of hMPV infection, six cynomolgus macaques (Macaca fascicularis) were inoculated with hMPV and examined by pathological and virological assays. They were euthanized at 5 (n 2) or 9 (n 2) days post-infection (dpi), or monitored until 14 dpi (n 2). Viral excretion peaked at 4 dpi and decreased to zero by 10 dpi. Viral replication was restricted to the respiratory tract and associated with minimal to mild, multi-focal erosive and inflammatory changes in conducting airways, and increased numbers of macrophages in alveoli. Viral expression was seen mainly at the apical surface of ciliated epithelial cells throughout the respiratory tract, and less frequently in type 1 pneumocytes and alveolar macrophages. Both cell tropism and respiratory lesions were distinct from those of SARS-associated coronavirus infection, excluding hMPV as the primary cause of SARS. This study demonstrates that hMPV is a respiratory pathogen and indicates that viral replication is short-lived, polarized to the apical surface, and occurs primarily in ciliated respiratory epithelial cells.

SOLUTION:
Short Communication Experimental Human Metapneumovirus Infection of Cynomolgus Macaques (Macaca fascicularis) Results in Virus Replication in Ciliated Epithelial Cells and Pneumocytes with Associated Lesions throughout the Respiratory Tract