The infection of host cells by HPIV2 triggers A-1210477 concentration some unknown mechanisms which initiate cell fusion process and these mechanisms seem to lead to up-regulation of host cell ADAM8, which might contribute to the cytopathic cell fusion. This suggests that

HPIV2 utilizes host encoded ADAM8 to spread from infected to non-infected target cells. On the cell surface, host cell fusion molecules, like ADAMs, could cause the HPIV2 infected host cell membrane to fuse with the neighboring non-infected cells to form syncytia. This strategy might enable fusion of dozens of non-infected cells to a giant multi-nuclear cell which means that HPIV2 can use resources of many more cells compared to an infection of only one cell although “”syncytial”" infected cells will lose viability much faster than do “”non-syncytial”" infected cells. At the same time, this syncytial virus factory protects against host-derived anti-viral antibodies,

complement and other host defense factors, unable to penetrate to the host target cell cytoplasm upon virus reproduction. However, expression of an ADAM8 protein in mononuclear prefusion cells and multinucleated cells does not mean that it functions as a fusion protein in this context although there is evidence for this in human osteoclastogenesis [17]. Conclusion This study demonstrates for the first time the up-regulation of ADAM8 during HPIV2 induced cell fusion. Using a Trojan horse strategy of this kind HPIV2 can spread efficiently and safely, possibly in part by utilizing the fusion IWR-1 mouse molecules of the host cells. Mammalian cell fusion has been studied Protein tyrosine phosphatase by others and by Temsirolimus molecular weight us in human monocyte cultures stimulated with receptor activator of nuclear factor kappa B ligand, which however is quite a time consuming and complicated system [18, 19]. It was therefore the aim of the present work to assess

if HPIV2 infected human cells have a potential to utilize also host cell fusion molecules in the fusion process as the first step towards the development of a novel tool for studying fusion of human cells although the characteristics of this system were not clarified by this work. Methods Cell cultures GMK, a kidney-derived epithelial-like cell line, is susceptible to HPIV2 and was maintained in virological laboratories to generate HPIV2 virions. It was obtained from the Helsinki University Central Hospital laboratory and maintained in minimal essential medium (MEM, HaartBio Ltd. Helsinki, Finland) containing 10% (v/v) heat-inactivated foetal bovine serum and 100 μg/l Glutamine-Penicillin-Streptomycin (HaartBio) in 75 cm2 culture flasks at 37°C and 5% CO2 incubator [20]. HSG cell line derived from human submandibular gland [21] and HSY cell line derived from human parotid gland [22] were cultured at 37°C, 5% CO2-in-air in Dulbecco’s modified Eagle’s medium with nutrient mixture F-12 Ham (DMEM/F-12, Sigma, St.