#Vector-delivered artificial #miRNA effectively inhibited replication of #Chikungunya virus (Antiviral Res., abstract)

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

Antiviral Res. 2016 Aug 23. pii: S0166-3542(16)30152-8. doi: 10.1016/j.antiviral.2016.08.019. [Epub ahead of print]

Vector-delivered artificial miRNA effectively inhibited replication of Chikungunya virus.

Saha A1, Bhagyawant S2, Parida M1, Dash PK3.

Author information: 1Virology Division, Defence Research & Development Establishment, Gwalior, 474002, India. 2Department of Biotechnology, Jiwaji University, Gwalior, India. 3Virology Division, Defence Research & Development Establishment, Gwalior, 474002, India. Electronic address: pabandash@drde.drdo.in.

 

Abstract

Chikungunya virus (CHIKV) has emerged as one of the most significant arboviral threats in many parts of the world. In spite of large scale morbidity, and long lasting polyarthralgia, no licensed vaccine or antivirals are available for the clinical management of CHIKV infection. In this study, a novel RNA interference based strategy has been adopted for effective inhibition of CHIKV. Four artificial microRNAs (amiRNAs) were designed to target different regions of CHIKV genome. These amiRNAs significantly inhibited CHIKV replication in Vero cells at both RNA and protein levels as assessed by qRT-PCR, immunoblotting and immunofluorescence techniques. Further inhibition of the infectious CHIKV up to 99.8% was demonstrated by plaque reduction assay. Concatemerization of amiRNA resulted in higher inhibition of CHIKV than individual amiRNAs. In addition, we studied the effect of combination of RNAi based therapy with other classical antivirals like chloroquine, ribavirin and mycophenolic acid, that helped in understanding the rational selection of RNAi based combination therapy. These findings provide a promising avenue for the development of novel amiRNA or combination based therapeutics against emerging CHIKV.

Copyright © 2016. Published by Elsevier B.V.

KEYWORDS: Antiviral drugs; Artificial miRNA; Chikungunya virus; GFP; RNAi

PMID: 27565991 DOI: 10.1016/j.antiviral.2016.08.019

[PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Chikungunya Fever; Antivirals.

——

How people react to #Zika virus #outbreaks on #Twitter? A computational content analysis (Am J Infect Control., abstract)

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

Am J Infect Control. 2016 Aug 24. pii: S0196-6553(16)30623-X. doi: 10.1016/j.ajic.2016.04.253. [Epub ahead of print]

How people react to Zika virus outbreaks on Twitter? A computational content analysis.

Fu KW1, Liang H1, Saroha N2, Tse ZT3, Ip P4, Fung IC5.

Author information: 1Journalism and Media Studies Centre, University of Hong Kong, Hong Kong. 2Department of Computer Science, University of Georgia, Athens, GA. 3College of Engineering, University of Georgia, Athens, GA. 4Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong. 5Department of Epidemiology, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA. Electronic address: cfung@georgiasouthern.edu.

 

Abstract

Zika-related Twitter incidence peaked after the World Health Organization declared an emergency. Five themes were identified from Zika-related Twitter content: (1) societal impact of the outbreak; (2) government, public and private sector, and general public responses to the outbreak; (3) pregnancy and microcephaly: negative health consequences related to pregnant women and babies; (4) transmission routes; and (5) case reports. User-generated contents sites were preferred direct information channels rather than those of the government authorities.

Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

KEYWORDS: Health communication; Zika virus disease; pregnancy complications; public response; social media

PMID: 27566874 DOI: 10.1016/j.ajic.2016.04.253

[PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Zika Virus; Society.

——

#Vaginal #Exposure to #Zika Virus during #Pregnancy Leads to #Fetal #Brain #Infection (Cell, abstract)

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

Cell. 2016 Aug 25;166(5):1247-1256.e4. doi: 10.1016/j.cell.2016.08.004.

Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection.

Yockey LJ1, Varela L2, Rakib T1, Khoury-Hanold W1, Fink SL3, Stutz B2, Szigeti-Buck K2, Van den Pol A4, Lindenbach BD5, Horvath TL2, Iwasaki A6.

Author information: 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520 USA. 2Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, 06520 USA. 3Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520 USA; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, 06520 USA. 4Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, 06520 USA. 5Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, 06520 USA. 6Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520 USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520 USA. Electronic address: akiko.iwasaki@yale.edu.

 

Abstract

Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS: antiviral defense; female reproductive tract; flavivirus; innate immunity; mucosal immunity; pattern recognition receptors; sexually transmitted infections; type I interferons

PMID: 27565347 DOI: 10.1016/j.cell.2016.08.004

[PubMed – in process]

Keywords: Research; Abstracts; Zika Virus; Pregnancy; Zika Congenital Infection.

——

#Polyclonal #IgM and #IgA block in vitro #complement deposition mediated by #antiganglioside #antibodies in autoimmune #neuropathies (Int Immunopharmacol., abstract)

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

Int Immunopharmacol. 2016 Aug 24;40:11-15. doi: 10.1016/j.intimp.2016.08.019. [Epub ahead of print]

Polyclonal IgM and IgA block in vitro complement deposition mediated by anti-ganglioside antibodies in autoimmune neuropathies.

Sudo M1, Miyaji K1, Späth PJ2, Morita-Matsumoto K3, Yamaguchi Y3, Yuki N4.

Author information: 1Department of Medicine Yong Loo Lin, School of Medicine, National University of Singapore, Singapore. 2Institute of Pharmacology, University of Bern, Switzerland. 3Structural Glycobiology Team, RIKEN, Japan. 4Department of Medicine Yong Loo Lin, School of Medicine, National University of Singapore, Singapore; Department of Physiology Yong Loo Lin, School of Medicine, National University of Singapore, Singapore. Electronic address: gbs.yuki.cidp@gmail.com.

 

Abstract

Intravenous immunoglobulin (IVIG), consisting of IgG, is the first-line treatment for Guillain-Barré syndrome and multifocal motor neuropathy. IgG, but neither IgM nor IgA, has been demonstrated in vitro to inhibit complement deposition mediated by anti-ganglioside autoantibodies in sera from patients with both conditions. The objective of this study is to investigate the in vitro effectiveness of IgM and IgA in inhibiting complement deposition to ganglioside/anti-ganglioside antibody complexes. Serum samples were obtained from patients with multifocal motor neuropathy associated with anti-GM1 IgM antibodies, Guillain-Barré syndrome associated with anti-GM1 IgG antibodies and Miller Fisher syndrome associated with anti-GQ1b IgG antibodies. Inhibition of complement deposition using different immunoglobulin preparations was measured by enzyme-linked immunosorbent assay. IgM/A-enriched IVIG and immunoglobulin isotypes (polyclonal IgM and IgA) showed higher potential in inhibiting complement deposition than standard IVIG. Although the safety concerns about the use of IgM and IgA for an immunotherapy still remain, IgM and IgA may serve as an alternative immunotherapy in those anti-ganglioside antibody-mediated neuropathies.

Copyright © 2016. Published by Elsevier B.V.

KEYWORDS: Anti-ganglioside antibody; Complement; Guillain–Barré syndrome; Intravenous immunoglobulin; Multifocal motor neuropathy

PMID: 27567246 DOI: 10.1016/j.intimp.2016.08.019

[PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Neurology; GBS; Serotherapy.

——

#Facial #Puffiness in a Returning #Traveler From #PuertoRico: #Chikungunya, #Dengue Fever, or #Zika Virus? (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Facial Puffiness in a Returning Traveler From Puerto Rico: Chikungunya, Dengue Fever, or Zika Virus?

Burke A. Cunha1,2, Anna Apostolopoulou1,2, Thulashie Sirarajah1,2, and Natalie C. Klein1,2

Author Affiliations: 1Infectious Disease Division, Winthrop University Hospital, Mineola; 2State University of New York, School of Medicine, Stony Brook, New York

Correspondence: B. A. Cunha, Infectious Disease Division, Winthrop University Hospital, 222 Station Plaza N (Ste 432) Mineola, NY 11501 (bacunha@winthrop.org).

_____

TO THE EDITOR—Clinical manifestations of Zika, dengue, and chikungunya infections have many features in common [1–7]. We report a case of Zika virus infection in a traveler returning from Puerto Rico, with fever, rash, myalgias/arthralgias initially thought to be dengue fever because of her facial puffiness and palatal petechiae.

A 41-year-old woman was admitted with fever, rash, headache, and myalgias/arthralgias for 4 days after returning to New York from Puerto Rico, where she reported multiple mosquito bites. One day before admission, a generalized nonpruritic maculopapular rash had developed. The patient reported fevers at home but she was afebrile on admission. Physical examination was remarkable for …

(…)

Keywords: Research; Abstracts; Zika Virus; Dengue Fever; Chikungunya Fever.

——

#Structures of #Ebola virus #GP and sGP in #complex with #therapeutic #antibodies (Nat Microbiol., abstract)

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

Nat Microbiol. 2016 Aug 8;1(9):16128. doi: 10.1038/nmicrobiol.2016.128.

Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

Pallesen J1, Murin CD1,2, de Val N1, Cottrell CA1, Hastie KM2, Turner HL1, Fusco ML2, Flyak AI3, Zeitlin L4, Crowe JE Jr3,5,6, Andersen KG1,2,7, Saphire EO2,8, Ward AB1.

Author information: 1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA. 2Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA. 3Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee 37232, USA. 4Mapp Biopharmaceutical, San Diego, California 92121, USA. 5Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232, USA. 6Vanderbilt Vaccine Center, Vanderbilt University, Nashville, Tennessee 37232, USA. 7Scripps Translational Institute, La Jolla, California 92122, USA.
8The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

 

Abstract

The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

PMID: 27562261 DOI: 10.1038/nmicrobiol.2016.128

[PubMed – in process]

Keywords: Research; Abstracts; Ebola.

——

#Codon #optimization of #antigen coding #sequences improves the immune potential of #DNA #vaccines against #avian #influenza virus #H5N1 in mice and chickens (Virol J., abstract)

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

Virol J. 2016 Aug 26;13(1):143. doi: 10.1186/s12985-016-0599-y.

Codon optimization of antigen coding sequences improves the immune potential of DNA vaccines against avian influenza virus H5N1 in mice and chickens.

Stachyra A1, Redkiewicz P1, Kosson P2, Protasiuk A1, Góra-Sochacka A1, Kudla G3, Sirko A4.

Author information: 1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland. 2Mossakowski Medical Research Centre Polish Academy of Sciences, ul., Pawinskiego 5, 02-106, Warsaw, Poland. 3MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, Scotland, UK. 4Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland. asirko@ibb.waw.pl.

 

Abstract

BACKGROUND:

Highly pathogenic avian influenza viruses are a serious threat to domestic poultry and can be a source of new human pandemic and annual influenza strains. Vaccination is the main strategy of protection against influenza, thus new generation vaccines, including DNA vaccines, are needed. One promising approach for enhancing the immunogenicity of a DNA vaccine is to maximize its expression in the immunized host.

METHODS:

The immunogenicity of three variants of a DNA vaccine encoding hemagglutinin (HA) from the avian influenza virus A/swan/Poland/305-135V08/2006 (H5N1) was compared in two animal models, mice (BALB/c) and chickens (broilers and layers). One variant encoded the wild type HA while the other two encoded HA without proteolytic site between HA1 and HA2 subunits and differed in usage of synonymous codons. One of them was enriched for codons preferentially used in chicken genes, while in the other modified variant the third position of codons was occupied in almost 100 % by G or C nucleotides.

RESULTS:

The variant of the DNA vaccine containing almost 100 % of the GC content in the third position of codons stimulated strongest immune response in two animal models, mice and chickens. These results indicate that such modification can improve not only gene expression but also immunogenicity of DNA vaccine.

CONCLUSION:

Enhancement of the GC content in the third position of the codon might be a good strategy for development of a variant of a DNA vaccine against influenza that could be highly effective in distant hosts, such as birds and mammals, including humans.

KEYWORDS: Chickens; DNA vaccine; GC content; H5N1; Influenza; Mice

PMID: 27562235 DOI: 10.1186/s12985-016-0599-y

[PubMed – in process]

Keywords: Research; Abstracts; Avian Influenza, H5N1; Vaccines.

—–