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3.
Preprint in English | bioRxiv | ID: ppbiorxiv-466755

ABSTRACT

There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by SARS-CoV-2, and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-seq examination identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation, and pulmonary fibrosis between HL grafts from infected and control NSG-L mice. Furthermore, when infecting humanized mice with human immune system (HIS) and autologous HL grafts (HISL mice), the mice had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-428920

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 100 million confirmed human infections, and 2 million more deaths globally since its emergence in the end of 2019. Several studies have shown that prior infection provided protective immunity against SARS-CoV-2 in non-human primate models. However, the effect of prior infection on blocking SARS-CoV-2 transmission is not clear. Here, we evaluated the impact of prior infection on protection and transmission of the SARS-CoV-2 virus in golden hamsters. Our results showed that prior infection provided protective immunity against SARS-CoV-2 re-challenge, but it was not sterizing immunity. The transmission experiment results showed that SARS-CoV-2 was efficiently transmitted from naive hamsters to prior infected hamsters by direct contact and airborne route, but not by indirect contact. Further, the virus was efficiently transmitted from prior infected hamsters to naive hamsters by direct contact, but not by airborne route and indirect contact. Surprisingly, the virus can be transmitted between prior infected hamsters by direct contact during a short period of early infection. Taken together, our study demonstrated that prior infected hamsters with good immunity can still be naturally re-infected, and the virus can be transmitted between prior infected hamsters and the naive through different transmission routes, implying the potential possibility of human re-infection and the risk of virus transmission between prior infected population and the healthy. Our study will help to calculate the herd immunity threshold more accurately, make more reasonable public health decisions, formulate an optimized population vaccination program, as well as aid the implementation of appropriate public health and social measures to control COVID-19.

5.
Sci Rep ; 9(1): 19734, 2019 12 24.
Article in English | MEDLINE | ID: mdl-31875046

ABSTRACT

H9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.


Subject(s)
Influenza A Virus, H9N2 Subtype , Mutation, Missense , Orthomyxoviridae Infections , Amino Acid Substitution , Animals , Dogs , Female , Guinea Pigs , Influenza A Virus, H9N2 Subtype/genetics , Influenza A Virus, H9N2 Subtype/metabolism , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/transmission
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-506006

ABSTRACT

Objective To evaluate the safety and efficiency of robot assisted surgery guided by damage control orthopaedics(DCO) in polytraumatised patients with pelvic ring injuries.Methods A retrospective review of the pelvic fracture database was performed.Twenty-six patients who had sustained a pelvic fracture from September 2012 to December 2015 were suitable for robot-assisted minimally invasive internal fixation.They were 17 men and 9 women,aged from 23 to 58 years (average,42.6 years).Their Injury Severity Score(ISS) ranged from 20 to 31 points (average,21.3 years).According to Tile classification,6 cases were type B2,3 type B3,9 type C2 and 8 type C3.Guided by DCO,the vital signs were stabilized by all means and the fractures treated by simple and temporary external fixation before the pelvic and other fractures were managed by the robot-assisted minimally invasive internal fixation.Demographics,times to operating room (TOR),time from acute stabilization to late definitive internal fixation (TAL),time for bone union,type of robot-assisted surgery for major fractures,length of stay (LOS),postoperative complications and mortality were recorded.The outcomes of the pelvis were evaluated at the final follow-up according to the Matta criteria.Results Of the 26 patients,robot-navigated percutaneous screwing was conducted with 23 sacroiliac screws in 19,with 9 ramus pubicus screws in 9,with 6 supraacetabular screws in 4,and with 4 both-column screws in 2 cases.TOR averaged 2.7 times,TAL 5.9 days,LOS at ICU 2.1 days,ICU admission rate 46.2% (12 of 26),hospital LOS 7.3 days,and time for pelvic bone union 79.0 days.None patients had postoperative complications related to the pelvic fracture and no one died.According to the Matta criteria at the final follow-ups,8 cases were excellent,11 good,5 fair and 2 poor,yielding an excellent and good rate of 73.1%.Conclusion Robot-navigated minimally invasive surgery plus DCO is effective,time saving and safe treatment for polytraumatised patients with pelvic ring injuries.

7.
Military Medical Sciences ; (12): 69-72, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-510397

ABSTRACT

Avian influenza virus is a new recombinant virus , which can cause severe respiratory symptoms ,such as short course,acute disease,and a high mortality rate.The purpose of this paper was to summarize the current status of this virus in terms of its epidemiology ,genetic evolution and virulence .By introducing the advancement in the research of this subtype virus, we hope to provide data and evidence ,for effective surveillance and prevention of this virus .

8.
Military Medical Sciences ; (12): 311-315, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-464095

ABSTRACT

Detection of pathogenic microorganisms has been a hot research field of microbiology.Conventional detection methods,such as isolation and culture, PCR technology, ELISA and genomic sequencing,are all time-consuming and com-plex.Because of the advantages of quick-testing, accuracy, safety and efficiency, spectroscopy has become a new non-inva-sive testing technology and has witnessed rapid development in pathogen detection and disease diagnosis.This article intro-duces three types of common spectroscopy technologies ( laser excitation fluorescence spectroscopy, infrared spectroscopy and Raman spectroscopy) , and also explains how they work in the detection of pathogenic microorganisms.

9.
Military Medical Sciences ; (12): 386-389, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-463388

ABSTRACT

Ebola virus disease , which can cause ebola hemorrhagic fever , is a potent zoonotic infectious virus disease . In 2014 , Ebola virus spread across West Africa and it has become a new major threat to global public health .This article summarizes the structural features of Ebola virus , transmission characteristics , interactions ,animal models .

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-595110

ABSTRACT

Objective To examine the heating capability of thermoseeds in isolated hepatic tissues.Methods Isolated hepatic tissues were heated uniformly to 37 ℃,meanwhile the thermoseeds and thermocouples were planted using a template paralleling with the magnetic line.Afterwards,the tissues were treated in an extracorporeal magnetic field of 120-123 gauss at a frequency of 113-116 kHz for 30 minutes.At the meantime,the temperature was recorded by a computer through thermocouples. Results The temperature of the tissues raised markedly with a largest change of 14 ℃.The heating area became hard and showed a gradual change of color(white-yellow-brown).The final temperature was negatively correlated with distance when using same number of the thermoseeds(r=-0.96017 to-0.99767,P=0.0023 to 0.0398),and positively correlated with the number of thermoseeds when measuring at a same point(r=0.93775 to 0.99270,P=0.0007 to 0.0185)except for the center group(r=0.93936,P=0.0606).Conclusions Thermoseeds inductive heating technology can achieve an appropriate temperature in isolated hepatic tissues.In certain extent,the temperature increase the number of thermoseeds and heating distance.

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