Enhancement of the Immune Response to Rabbit Hemorrhagic Disease Vaccine in Young Rabbits by Advanced Vaccination and Chinese Herbal Adjuvants

Experiments were conducted to determine the effects of advanced vaccination and Chinese herbal adjuvants （CHA）, containing astragalus polysaccharides （APS） and ginsenosides （GS） on the immune response to rabbit hemorrhagic disease （RHD） vaccine in young rabbits. In experiment 1, 5 New Zealand rabbits of each group at 30, 35, 40, or 45 days of age were injected with 2 mL of inactivated RHD vaccine, respectively. The dynamic changes of antibody titers were tested by the hemagglutination inhibition （HI） method. In experiment 2, 30 New Zealand rabbits at 35 days of age were randomly assigned to 5 treatment groups, representing inoculation with 3 mL of non-adjuvant RHD vaccine, CHA-RHD vaccine, CHA-HA vaccine （half dose antigen）, aluminium adjuvant-RHD vaccine, and PBS, respectively. The dynamic changes of peripheral lymphocyte proliferation and serum antibody titers were tested by the MTT method and the HI method. The results showed that the titer of maternal HI antibody in the 35-day-old rabbits was lower than the protective level of 3 log2, while on days 7 to 49 after the vaccination, the antibody titers were higher than 3 log2. The CHA promoted the lymphocyte proliferation and enhanced the serum antibody titer （P〈 0.05）. These findings from the two experiments suggested that advanced vaccination and Chinese herbal adjuvants significantly enhanced the immune response to vaccine against RHD, and effectively protected the young rabbits against RHD challenge.

Diagnosis and Control of Rabbit Hemorrhagic Disease(RHD)

In this study, chronic-type rabbit hemorrhagic disease occurred in rabbit warrens of Shandong, Liaoning, Beijing and Hebei, which was mainly charac-terized by deaths of young and adult rabbits, longer durationand nerve symptoms, was surveyed by epidemiological investigation, bacterial isolation and incubation, artificial infection test and histopathologieal method to analyze the causes of chronic-type rabbit hemorrhagic disease and put forward the corresponding control measures.

Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus

Rabbit hemorrhagic disease was described in China in 1984 and can cause hemorrhagic necrosis of the liver within two or three days after infection.The etiological agent,rabbit hemorrhagic disease virus(RHDV),belongs to the Lagovirus genus in the Caliciviridae family.Compared to other calicivirus,such as rNV and SMSV,the structure of Lagovirus members is not well characterized.In this report,structures of two types of wild RHDV particles,the intact virion and the core-like particle(CLP),were reconstructed by cryo-electron microscopy at 11Åand 17Å,respectively.This is the first time the 3D structure of wild caliciviruses CLP has been provided,and the 3D structure of intact RHDV virion is the highest resolution structure in Lagovirus.Comparison of the intact virion and CLP structures clearly indicated that CLP was produced from the intact virion with the protrusion dissociated.In contrast with the crystal structures of recombinant Norovirus and San Miguel sea lion virus,the capsomers of RHDV virion exhibited unique structural features and assembly modes.Both P1 and P2 subdomains have interactions inside the AB capsomer,while only P2 subdomains have interaction inside CC capsomer.The pseudo atomic models of RHDV capsomers were constructed by homology modeling and density map fitting,and the rotation of RHDV VP60 P domain with respect to its S domain,compared with SMSV,was observed.Collectively,our cryo-electron microscopic studies of RHDV provide close insight into the structure of Lagovirus,which is important for functional analysis and better vaccine development in the future.

A serologic investigation of epizootic hemorrhagic disease virus in China between 2014 and 2019

Epizootic hemorrhagic disease virus(EHDV)is a member of the genus Orbivirus,family Sedoreoviridae.It was firstly recognized in 1955 to cause a highly fatal disease of wild white-tailed deer in America.So far,EHDV was detected and isolated in many wild or domestic ruminants,and widely distributed all over the world.Although the domestic cattle and sheep infected by EHDV were usually asymptomatic or subclinical,several outbreaks of epizootic hemorrhagic disease(EHD)in deer and cattle had been reported.Many EHDV strains were isolated and sequenced in last two decades in China,which promoted a general serologic investigation of EHDV in China.In this study,18,122 sera were collected from asymptomatic or subclinical domestic ruminants(cattle,cow,yaks,sheep,goats,and deer)in 116 regions belonging to 15 provinces in China.All the sera were tested by EHDV CELISA,and the results were obtained by big data analysis.EHDV infections were detected in the 14 of 15provinces,and only Tibet(average altitude≥4000 m)which was the highest province in China was free of EHDV.The numbers of seropositive collections in both bovine and goat/sheep were in an inverse proportion to the latitude.However,the seropositive rates in bovine were ranged from 0%to 100%,while the seropositive rates in goat/sheep were no more than 50%.The results suggested that bovine was obviously more susceptive for EHDV infection than goat and sheep,therefore might be a major reservoir of EHDV in China.The prevalence of EHDV was consistent with the distribution of Culicoides which were known as the sole insect vectors of EHDV.In particular,the seropositive rates of EHDV were very high in the southern provinces,which required the enhanced surveillance in the future.

Nucleolin interacts with the rabbit hemorrhagic disease virus replicase RdRp, nonstructural proteins p16 and p23, playing a role in virus replication

Rabbit hemorrhagic disease virus(RHDV)is a member of the Caliciviridae family and cannot be propagated in vitro,which has impeded the progress of investigating its replication mechanism.Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells.Here,aided by this replicon system and using two-step affinity purification,we purified the RHDV replicase and identified its associated host factors.We identified rabbit nucleolin(NCL)as a physical link,which mediating the interaction between other RNA-dependent RNA polymerase(Rd Rp)-related host proteins and the viral replicase Rd Rp.We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV replication in RK-13 cells,respectively.NCL was identified to directly interact with RHDV Rd Rp,p16,and p23.Furthermore,NCL knockdown severely impaired the binding of Rd Rp to Rd Rp-related host factors.Collectively,these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link between viral replicase and host proteins.

Susceptibility-Weighted MRI in the Evaluation of Gynecologic Diseases

Introduction: Owing to the advanced development of MRI science, it causes obvious great changes of many diseases that affect the female genital system and affect their fertility. Hemorrhagic gynecological diseases especially endometriosis affect young females and cause cyclic pain, in addition to infertility. So early detection is essential for proper treatment. Susceptibility-weighted (SWI) as one of the most recent newly created MRI sequences is highly sensitive to detect products of hemorrhage within different gynecologic disorders with 94.7% sensitivity being more meticulous than conventional MRI sequences as T1 and T2. Aim of the Work: A comparison between T1 and T2 as conventional MRI sequences with susceptibility-weighted images (SWI) in many gynecologic disorders by the detection of the presence of internal products of hemorrhage at any stage. Subjects and Methods: 48 consecutive patients from Benha University clinics (age range, 17 - 60 years;mean age, 35.67 years). The patients included in the study were presenting with pelvic pain, irregular menses, Dyspareunia, and swelling. All with suspicious diagnosis of ovarian and extra-ovarian lesions. 38 patients out of the 48 patients were known to contain hemorrhagic disorder;all the patients underwent MRI routine pelvis protocol adding SWI sequence. Results: There was a greatly significant difference between SWI and conventional MRI sequences T1and T2 with sensitivity 94.7%, 57.9% and 33.3% respectively. Conclusion: SWI is a promising tool in the evaluation of hemorrhagic foci within different gynecological disorders. The great ability of detecting hemosiderin foci increases the value of SWI over conventional MRI or US.

Silencing the gene encoding C/EBP homologous protein lessens acute brain injury following ischemia/reperfusion

C/EBP homologous protein, an important transcription factor during endoplasmic reticulum stress, participates in cell apoptosis mediated by endoplasmic reticulum stress. Previous studies have shown that C/EBP homologous protein mediates nerve injury during Alzheimer＇s disease, subarachnoid hemorrhage and spinal cord trauma. In this study, we introduced C/EBP homologous protein short hairpin RNA into the brains of ischemia/reperfusion rat models via injection of lentiviral vector through the left lateral ventricle. Silencing C/EBP homologous protein gene expression significantly reduced cerebral infarction volume, decreased water content and tumor necrosis factor-α and interleukin-1β mRNA expression in brain tissues following infarction, diminished the number of TUNEL-positive cells in the infarct region, decreased caspase-3 protein content and increased Bcl-2 protein content. These results suggest that silencing C/EBP homologous protein lessens cell apoptosis and inflammatory reactions, thereby protecting nerves.

A review on the Ebola virus,outbreak history and the current research tools to control the disease

The Ebola virus is a zoonotic pathogen causing hemorrhagic fever disease with a high mortality rate.The distribution of this pathogen has been limited to woodlands from Central and West Africa and the forest-savannah ecotone in East Africa.The likely reservoir species are frugivorous bats living in these areas.This pathogen is becoming an increasing threat to human populations since its distribution range is expanding faster than expected.The current Ebola outbreaks in Western Africa and in the Democratic Republic of Congo have rapidly spread infecting high numbers of individuals in five African countries.The disease has reached the United States and Spain.This expansion is due partly to increasing global connectivity.This situation represents a new challenge to control the spread of the disease.Experimental drugs have been used to treat a few infected people with promising results.This gives hope for an effective treatment against Ebola hemorrhagic fever in the near future,though thousands of people remain at risk of infection.The present review aims to give an update of the knowledge on the disease,including features of the Ebola virus,the history of disease outbreaks in Africa and the tools that are being developed in order to control this re-emergent disease.