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-α. Since TNF-α 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-α. 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-α, 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: Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk22/2 cells, but not Jnk12/2 cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk72/2) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk22/2 mice, but not Jnk12/2 mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.

SOLUTION: MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection

PROBLEM: Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1 st or the 3 rd position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3 rd position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV-and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.

SOLUTION:
Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350