Crystal structure of the C-terminal fragment of NS1 protein from yellow fever virus

Dear Editor,Yellow fever（YF）,a mosquito-borne flavivirus disease,is endemic in tropical areas of Africa and Central and South America.YF is transmitted via the bite of infected Aedes aegypti or Haemogogus mosquitoes and mainly affects humans and nonhuman primates.

Generation and Application of a Luciferase Reporter Virus Based on Yellow Fever Virus 17D

Yellow fever virus(YFV) is a re-emerging virus that can cause life-threatening yellow fever disease in humans.Despite the availability of an effective vaccine,little is known about the replication mechanism of YFV,and there are still no available specific anti-YFV medicines.Herein,by introducing the Renilla luciferase gene(Rluc) into an infectious clone of YFV vaccine strain 17 D,we generated a recombinant virus 17 D-Rluc.2 A via reverse genetics approaches.The 17 D-Rluc.2 A had similar plaque morphology and comparable in vitro growth characteristics with its parental strain.Importantly,the reporter luciferase was efficiently expressed in 17 D-Rluc.2 A-infected mammalian and mosquito cells,and there was a good linear correlation between intracellular luciferase expression and extracellular infectious virion reproduction.Furthermore,by a combination of the 17 D-Rluc.2 A reporter virus and selective 2’-hydroxyl acylation analyzed by primer extension(SHAPE)technology,the conserved 5’-SLA element was shown to be essential for YFV replication,highlighting the capability of17 D-R1 uc.2 A in the investigation of YFV replication.At last,we demonstrated that two compounds with distinct anti-viral mechanisms can effectively inhibit the viral propagation in 17 D-Rluc.2 A-infected cells,demonstrating its potential application in the evaluation of anti-viral medicines.Taken together,the 17 D-Rluc.2 A serves as a useful tool for the study of YFV replication and anti-YFV medicine development.

Acute Kidney Injury (AKI) in the Setting of Multi-Organ Dysfunction Syndrome (MODS) Secondary to Yellow Fever Infection (YFI) in a 19-Year-Old Woman

Background: Outbreak of yellow fever infection (YFI), a mosquito-borne disease, occurs sporadically worldwide especially in tropical nations. Acute kidney injury (AKI) commonly results from YFI and could be associated with a poor prognosis for victims even under intensive care unit (ICU). Pathophysiologic mechanisms for AKI include hypovolemic shut down, cytotoxicity, acute tubular necrosis (ATN), hemolysis, or coagulopathy. Early diagnosis, prompt and effective treatment modalities including dialysis improve treatment outcome. Aim: We report the case management of a 19-year-old woman who had yellow fever infection complicated by acute kidney injury in the setting of multi-organ dysfunction syndrome (MODS). Case Presentation: A 19-year-old woman who presented with fever, headache and vomiting for 2 weeks. In the course of the illness, urine volume became reduced and coke colored, followed by body swelling, yellowness of the eyes bleeding from the orifices. Examination revealed an acutely ill looking woman, icteric, and with pedal edema. Her pulse was 100/min and blood pressure was 120/80 mmHg. Liver was enlarged, soft and tender. She had proteinuria 3+ and polymerase chain reaction (PCR) confirmed yellow fever infection. She had markedly deranged serum biochemical parameters for which she had a three-hour session of hemodialysis with Heparin anticoagulation. The urea reduction ratio (URR) was 46.9%. Barrier nursing was commenced. She had 7 units of whole blood and a pint of fresh frozen plasma (FFP) with antibiotics, Rabeprazole, Tranexamic acid, Vitamin K and Frusemide. She had the second dialysis session of HD and entered into the recovering phase of AKI and was subsequently discharged after 18th days on admission. Conclusion: Yellow fever infection occurs sporadically and could lead to MODS involving the kidneys, liver and hematologic system. Prompt initiation of dialysis, correction of coagulopathy, and antibiotics use are measures needed to arrest progression and death. Vaccination, destruction of the natural habitat of the carrier and infective organisms are necessary particularly in endemic regions of the world.