A Preliminary Study On The Interaction Between Hemorrhagic Fever Virus Proteinsand Human Proteins

Hemorrhagic fever is an important infectious disease hazards to human health,namely epidemic hemorrhagic fever, also known as hemorrhagic fever with renalsyndrome, which caused by a virus infection in rodents as the main source of naturalfoci of disease. The pathogen is a virus, belongs to Bunyaviridae, called Hantavirusgenus. Hantavirus is a single-stranded negative-RNA, divided into three differentfragments: large (L), medium (M), small (S), encoding polymerase (L protein),envelope glycoproteins (G1and G2protein), and nucleoprotein (NP protein)respectively.As we all know, the interactions between pathogens and host proteins are thebasis for the occurrings of infectious diseases. The studies had already been carriedout on the interactions between pathogens and host, such as Helicobacter pylori,herpes virus, malaria parasites, plague bacteria, viral hepatitis, influenza virus. Andthere is no reports about the PPI between HFRS and host, its pathogenesis is not clear.Therefore it is necessary to carry out the research on the protein interaction networkbetween HFRS and host for improving the prevention and treatment of hemorrhagicfever.AMRV H8205G2protein was used as the bait and successfully screened againsthuman spleen cDNA library. Over211candidate colonies were isolated initially, andafter removal of sequences mapping to the non-coding DNA region and the codingsequence out of AD frame,177cDNA fragments were retained in our data set. Toestimate our technical false positive rate, all interactions were verified byreassessment of the interactions in yeast cells. The total recovery for all theinteractions was85%. We have used several independent bioinformatics analysis toevaluate the potential biological relevance of the identified interactions.Nuclear transcription factor κB (NF-κB) is a critical transcription factor, whichregulated immune and inflammation signaling pathways in response to environmentalchanges and involved in cell adhesion, growth, differentiation and apoptosis.Ribosomal protein S3(RPS3) is a subunit of NF-kB and regulates the transcription ofspecific target genes directly.Here, by using a yeast two-hybrid technology, RPS3was identified as a partnerof G2. We show that G2physically associated with RPS3in vivo and in vitro.Overexpression of G2increased NF-κB-dependent transcription and NF-κBdownstream target genes expressions. Simultaneously, G2could promote RPS3phosphorylation and nuclear translocation by enhancing the interaction between RPS3and IKKβ/Imp-α.In summary, G2activated NF-κB signaling pathway and affected the downstream target genes mRNA levels by enhancing the phosphorylation of RPS3, whichcontributed the nucleus translocation of RPS3. Our results suggested that theinteraction between G2and RPS3plays a vital role in the pathogenesis ofhemorrhagic fever viruses which provided a new theory and idea for the preventionand treatment of hemorrhagic fever in the molecular level.