#Repurposing #Quinacrine Against #Ebola Virus Infection In vivo (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Repurposing Quinacrine Against Ebola Virus Infection In vivo

Thomas R. Lane, Jason E. Comer, Alexander N. Freiberg, Peter B. Madrid, Sean Ekins

DOI: 10.1128/AAC.01142-19

 

ABSTRACT

Quinacrine hydrochloride is a small-molecule, orally bioavailable drug that has been used clinically as an antimalarial and for many other applications. A machine learning model trained on Ebola virus (EBOV) screening data identified quinacrine as a potent (nM) in vitro inhibitor. Quinacrine (25 mg/kg) was shown in the current study to protect 70% of mice (statistically significant) from a lethal challenge with mouse-adapted EBOV (maEBOV) with once daily intraperitoneal (i.p.) dosing for 8 days.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Ebola; Quinacrine; Animal models.

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A novel #H7N3 #reassortant originating from the zoonotic #H7N9 highly pathogenic #avian #influenza viruses that has adapted to #ducks (Transbound Emerg Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transbound Emerg Dis. 2019 Jul 11. doi: 10.1111/tbed.13291. [Epub ahead of print]

A novel H7N3 reassortant originating from the zoonotic H7N9 highly pathogenic avian influenza viruses that has adapted to ducks.

Nakayama M1, Uchida Y1, Shibata A2, Kobayashi Y3, Mine J1, Takemae N1, Tsunekuni R1, Tanikawa T1, Harada R2, Osaka H2, Saito T1,4.

Author information: 1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. 2 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Tokoname, Aichi, 479-0881, Japan. 3 Pathological and Physiochemical Examination Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Yokohama, Kanagawa, 235-0008, Japan. 4 United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.

 

Abstract

The first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in March 2013 in China. This virus continues to circulate in poultry in China while mutating to highly pathogenic AIVs (HPAIVs). Through monitoring at airports in Japan, a novel H7N3 reassortant of the zoonotic H7N9 HPAIVs, A/duck/Japan/AQ-HE30-1/2018 (HE30-1), was detected in a poultry meat product illegally brought by a passenger from China into Japan. We analyzed the genetic, pathogenic, and antigenic characteristics of HE30-1 by comparing it with previous zoonotic H7N9 AIVs and their reassortants. Phylogenetic analysis of the entire HE30-1 genomic sequence revealed that it comprised at least three different sources; the HA (H7), PB1, PA, NP, M, and NS segments of HE30-1 were directly derived from H7N9 AIVs, whereas the NA (N3) and PB2 segments of HE30-1 were unrelated to zoonotic H7N9. Experimental infection revealed that HE30-1 was lethal in chickens but not in domestic or mallard ducks. HE30-1 was shed from and replicated in domestic and mallard ducks and chickens, whereas previous zoonotic H7N9 AIVs have not adapted well to ducks. This finding suggests the possibility that HE30-1 may disseminate to remote area by wild bird migration once it establishes in wild bird population. A hemagglutination-inhibition assay indicated that antigenic drift has occurred among the reassortants of zoonotic H7N9 AIVs; HE30-1 showed similar antigenicity to some of those H7N9 AIVs, suggesting it might be prevented by the H5/H7 inactivated vaccine that was introduced in China in 2017. Our study reports the emergence of a new reassortant of zoonotic H7N9 AIVs with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.

This article is protected by copyright. All rights reserved.

KEYWORDS: adaptation to ducks; animal experiments; novel H7N3 reassortant; zoonotic H7N9 avian influenza viruses

PMID: 31293102 DOI: 10.1111/tbed.13291

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Animal models.

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#Age-associated #changes in the #impact of #sex #steroids on #influenza #vaccine responses in males and females (npj Vaccines, abstract)

[Source: npj Vaccines, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 12 July 2019

Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females

Tanvi Potluri, Ashley L. Fink, Kristyn E. Sylvia, Santosh Dhakal, Meghan S. Vermillion, Landon vom Steeg, Sharvari Deshpande, Harish Narasimhan & Sabra L. Klein

npj Vaccines, volume 4, Article number: 29 (2019)

 

Abstract

Vaccine-induced immunity declines with age, which may differ between males and females. Using human sera collected before and 21 days after receipt of the monovalent A/Cal/09 H1N1 vaccine, we evaluated cytokine and antibody responses in adult (18–45 years) and aged (65+ years) individuals. After vaccination, adult females developed greater IL-6 and antibody responses than either adult males or aged females, with female antibody responses being positively associated with concentrations of estradiol. To test whether protection against influenza virus challenge was greater in females than males, we primed and boosted adult (8–10 weeks) and aged (68–70 weeks) male and female mice with an inactivated A/Cal/09 H1N1 vaccine or no vaccine and challenged with a drift variant A/Cal/09 virus. As compared with unvaccinated mice, vaccinated adult, but not aged, mice experienced less morbidity and better pulmonary viral clearance following challenge, regardless of sex. Vaccinated adult female mice developed antibody responses that were of greater quantity and quality and more protective than vaccinated adult males. Sex differences in vaccine efficacy diminished with age in mice. To determine the role of sex steroids in vaccine-induced immune responses, adult mice were gonadectomized and hormones (estradiol in females and testosterone in males) were replaced in subsets of animals before vaccination. Vaccine-induced antibody responses were increased in females by estradiol and decreased in males by testosterone. The benefit of elevated estradiol on antibody responses and protection against influenza in females is diminished with age in both mice and humans.

Keywords: Seasonal Influenza; Vaccines; Animal models.

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#Avian #Influenza #H5N6 Viruses Exhibit Differing #Pathogenicities and #Transmissibilities in #Mammals (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2017 Nov 24;7(1):16280. doi: 10.1038/s41598-017-16139-1.

Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals.

Zhao Z1, Guo Z1, Zhang C1, Liu L1, Chen L2, Zhang C2, Wang Z1, Fu Y1, Li J1, Shao H3, Luo Q4, Qian J5, Liu L6.

Author information: 1 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. 2 College of Veterinary Medicine, Hebei Agricultural University, 2596 lucky south street, Baoding, 071000, Hebei, China. 3 Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China. 4 Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China. qingping0523@163.com. 5 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. qianj1970@126.com. 6 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. liulinna7@126.com.

Erratum in Author Correction: Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals. [Sci Rep. 2018]

 

Abstract

Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses. These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health.

PMID: 29176564 PMCID: PMC5701206 DOI: 10.1038/s41598-017-16139-1 [Indexed for MEDLINE]  Free PMC Article

Keywords: Avian Influenza; H5N6; H6N6; Reassortant strain; Poultry; Human; Animal models.

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Repeated #vaccination against matched #H3N2 #influenza virus gives less #protection than single vaccination in ferrets (npj Vaccines, abstract)

[Source: npj Vaccines, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 09 July 2019

Repeated vaccination against matched H3N2 influenza virus gives less protection than single vaccination in ferrets

Nedzad Music, Wen-Pin Tzeng, F. Liaini Gross, Min Z. Levine, Xiyan Xu, Wun-Ju Shieh, Terrence M. Tumpey, Jacqueline M. Katz & Ian A. York

npj Vaccines, volume 4, Article number: 28 (2019)

 

Abstract

Epidemiological studies suggest that humans who receive repeated annual immunization with influenza vaccine are less well protected against influenza than those who receive vaccine in the current season only. To better understand potential mechanisms underlying these observations, we vaccinated influenza-naive ferrets either twice, 10 months apart (repeated vaccination group; RV), or once (current season only group; CS), using a prime-boost regimen, and then challenged the ferrets with A/Hong Kong/4801/2014(H3N2). Ferrets that received either vaccine regimen were protected against influenza disease and infection relative to naive unvaccinated ferrets, but the RV group shed more virus, especially at the peak of virus shedding 2 days post infection (p < 0.001) and regained weight more slowly (p < 0.05) than those in the CS group. Qualitative, rather than quantitative, differences in the antibody response may affect protection after repeated influenza vaccination.

Keywords: Seasonal Influenza; H3N2; Vaccines; Animal models.

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#Human Polyclonal #Antibodies Prevent Lethal #Zika Virus #Infection in Mice (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 08 July 2019

Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Emilie Branche, Ayo Yila Simon, Nicholas Sheets, Kenneth Kim, Douglas Barker, Anh-Viet T. Nguyen, Harpreet Sahota, Matthew Perry Young, Rebecca Salgado, Anila Mamidi, Karla M. Viramontes, Trevor Carnelley, Hongyu Qiu, Annie Elong Ngono, Jose Angel Regla-Nava, Mercylia Xevana Susantono, Joan M. Valls Cuevas, Kieron Kennedy, Shantha Kodihalli & Sujan Shresta

Scientific Reports, volume 9, Article number: 9857 (2019)

 

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that represents a major threat to global health. ZIKV infections in adults are generally asymptomatic or present with mild symptoms. However, recent outbreaks of ZIKV have revealed that it can cause Congenital Zika Syndrome in neonates and Guillain-Barré syndrome in adults. Currently, no ZIKV-specific vaccines or antiviral treatments are available. In this study, we tested the efficacy of convalescent plasma IgG hyperimmune product (ZIKV-IG) isolated from individuals with high neutralizing anti-ZIKV titers as a therapeutic candidate against ZIKV infection using a model of ZIKV infection in Ifnar1−/− mice. ZIKV-IG successfully protected mice from lethal ZIKV challenge. In particular, ZIKV-IG treatment at 24 hours after lethal ZIKV infection improved survival by reducing weight loss and tissue viral burden and improving clinical score. Additionally, ZIKV-IG eliminated ZIKV-induced tissue damage and inflammation in the brain and liver. These results indicate that ZIKV-IG is efficacious against ZIKV, suggesting this human polyclonal antibody is a viable candidate for further development as a treatment against human ZIKV infection.

Keywords: Zika Virus; Serotherapy; Animal models.

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#PB2 and #hemagglutinin #mutations confer a #virulent #phenotype on an #H1N2 #avian #influenza virus in mice (Arch Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Virol. 2019 Aug;164(8):2023-2029. doi: 10.1007/s00705-019-04283-0. Epub 2019 May 20.

PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice.

Yu Z1, Ren Z2, Zhao Y3, Cheng K4, Sun W3, Zhang X3, Wu J5, He H6, Xia X7, Gao Y8.

Author information: 1 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China. zhijun0215@gmail.com. 2 Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China. 3 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. 4 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 5 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China. 6 College of Life Sciences, Shandong Normal University, Jinan, 250014, China. 7 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. xiaxzh@cae.cn. 8 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China. gaoyuwei@gmail.com.

 

Abstract

We previously obtained mouse-adapted variants of H1N2 avian influenza virus that contained PB2-L134H, PB2-I647L, PB2-D701N, HA-G228S, and M1-D231N mutations. Here, we analyzed the effects of these mutations on viral pathogenicity in a mammalian model. By evaluating the virulence of mouse-adapted H1N2 variants at different generations, we found that the PB2-D701N and HA-G228S mutations both contribute to the virulence of this virus in mammals. Furthermore, we found that the PB2-D701N and HA-G228S mutations both enhance the ability of the virus to replicate in vivo and in vitro and that the PB2-D701N substitution results in an expansion of viral tissue tropism. These results suggest that the PB2-D701N mutation and the HA-G228S mutation are the major mammalian determinants of H1N2 virus. These results help us to understand more about the mechanisms by which influenza viruses adapt to mammals, and monitoring of these mutations can be used in continuous influenza surveillance to assess the pandemic potential of avian influenza virus variants.

PMID:  31111259  DOI:  10.1007/s00705-019-04283-0 [Indexed for MEDLINE]

Keywords: Avian Influenza; H1N2; Animal models.

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