The emerging influenza virus threat: status and new prospects for its therapy and control

Kumar, Binod; Asha, Kumari; Khanna, Madhu; Ronsard, Larance; Meseko, Clement; Sanicas, Melvin

doi:10.1007/s00705-018-3708-y

Cited by 78 publications

(59 citation statements)

References 123 publications

(145 reference statements)

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“…2c). The calculated half time of recovery was 2.9 seconds and the diffusion rate calculated was 2.422 ± 0.154 m -13 s -1 (D ± SEM), a value similar to what has been found for other liquid organelles including Negri bodies formed during rabies virus infection 27 . These measurements are also consistent with those of nucleoli and stress granules 27,36 , indicating that viral inclusions exchange material with similar structures or with the cytosol.…”

Section: Resultssupporting

confidence: 84%

See 1 more Smart Citation

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

Alenquer

Vale-Costa

Sousa

et al. 2018

Preprint

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18Influenza A virus has an eight-partite RNA genome that during viral assembly forms a 19 supramolecular complex containing one copy of each RNA. Genome assembly is a selective 20 process driven by RNA-RNA interactions and is thought to lead to discrete punctate structures 21 scattered through the cytosol. Here, we show that contrary to the accepted view, formation of 22 these structures is not dependent on RNA-RNA interactions among distinct viral 23 ribonucleoproteins (vRNPs), as they assemble in cells expressing only one vRNP type. We 24 demonstrate that these viral inclusions display characteristics of liquid organelles, segregating 25 from the cytosol without a delimitating membrane, dynamically exchanging material, deforming 26 easily and adapting fast to hypotonic shock. We provide evidence that they develop close to the 27 Endoplasmic Reticulum Exit Sites (ERES), being dependent on continuous ER-Golgi vesicular 28cycling. We show that viral inclusions do not promote escape to interferon response, and 29 propose that they facilitate selected RNA-RNA interactions in a liquid environment of 30 concentrated vRNPs. 31 32 33 34 3 MAIN TEXT 35 Influenza A infections are serious threats to human health causing annual epidemics and 36 occasional pandemics 1 . The virus contains an eight-partite RNA genome, and each segment is 37 encapsidated as an individual viral ribonucleoprotein (vRNP) complex. vRNPs are composed of 38 single-stranded negative-sense RNA, with base paired terminal sequences originating a double 39 stranded RNA portion where the trimeric RNA-dependent RNA polymerase (RdRp), composed 40 of PB1, PB2 and PA, binds. The remaining sequence attaches several copies of unevenly-41 bound nucleoprotein (NP) 2 . The advantages of having a segmented genome are evident for 42 viral evolution 3 and for better gene expression control 4 , but increase the complexity of the 43 assembly of fully infectious virions 5-8 . 44 Viral assembly occurs at the plasma membrane and, in 80% of the cases, 8 distinct 45 vRNPs are packaged selectively into a budding membrane 9 . Seminal work established the 46 requirement of cis-acting and intersegment RNA-RNA interactions for the formation of this 47 supra-molecular complex (reviewed in 5-8 ). However, it is under debate if vRNPs reach the 48 plasma membrane already as complete genome bundles. 49Upon exiting the nucleus, where they replicate, vRNPs accumulate around the 50 microtubule organizing centre 10 and, subsequently, distribute throughout the cytoplasm 51 concentrating in discrete puncta that enlarge as infection progresses 10-14 . Each puncta 52 accommodates different vRNP segments with the diversity in vRNPs increasing proportionally to 53 the proximity of the plasma membrane 11,13 . Such observation led to the proposal that genome 54 assembly preceded vRNP packaging in budding virions by a process intimately linked with the 55 formation of the referred vRNP hotspots 6,11,[13][14][15] . Studies on the biogenesis of vRNP hotspots 56 showed that their formation requires...

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Section: Resultssupporting

confidence: 84%

“…Influenza A infections are serious threats to human health causing annual epidemics and occasional pandemics 1 . The virus contains an eight-partite RNA genome, and each segment is encapsidated as an individual viral ribonucleoprotein (vRNP) complex.…”

Section: Main Textmentioning

confidence: 99%

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

Alenquer

Vale-Costa

Sousa

et al. 2018

Preprint

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“…Critically ill patients are characterized by a variety of conditions that may alter drug absorption, like altered gastrointestinal motility, and pharmacokinetics, such as the need for renal replacement therapy or extracorporeal membrane oxygenation. Furthermore, in mechanically ventilated patients, administration of inhaled zanamivir is contraindicated because of reported fatal complications, and oseltamivir has to be administered via nasogastric tube [6]. The IDSA recommends against the routine use of higher doses of Food and Drug Administration (FDA)-approved NAI drugs for therapy of seasonal influenza [5].…”

Section: Introductionmentioning

confidence: 99%

Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials

2020

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“…These vaccines, however, cannot effectively protect against newly emerging viruses with antigenic shift and drift. 108,109 Antigenic drift results in changes in the antigenic site (a minor change) while antigenic shift results in a new virus subtype. Hemagglutinin and neuraminidase are the two enzymes dictating the antigenic properties of the viruses.…”

Section: Influenza Virusmentioning

confidence: 99%

<p>Immunoinformatics and Vaccine Development: An Overview</p>

Oli

Obialor

Ifeanyichukwu

et al. 2020

ITT

177

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The use of vaccines have resulted in a remarkable improvement in global health. It has saved several lives, reduced treatment costs and raised the quality of animal and human lives. Current traditional vaccines came empirically with either vague or completely no knowledge of how they modulate our immune system. Even at the face of potential vaccine design advance, immune-related concerns (as seen with specific vulnerable populations, cases of emerging/reemerging infectious disease, pathogens with complex lifecycle and antigenic variability, need for personalized vaccinations, and concerns for vaccines' immunological safety -specifically vaccine likelihood to trigger non-antigen-specific responses that may cause autoimmunity and vaccine allergy) are being raised. And these concerns have driven immunologists toward research for a better approach to vaccine design that will consider these challenges. Currently, immunoinformatics has paved the way for a better understanding of some infectious disease pathogenesis, diagnosis, immune system response and computational vaccinology. The importance of this immunoinformatics in the study of infectious diseases is diverse in terms of computational approaches used, but is united by common qualities related to host-pathogen relationship. Bioinformatics methods are also used to assign functions to uncharacterized genes which can be targeted as a candidate in vaccine design and can be a better approach toward the inclusion of women that are pregnant into vaccine trials and programs. The essence of this review is to give insight into the need to focus on novel computational, experimental and computation-driven experimental approaches for studying of host-pathogen interactions and thus making a case for its use in vaccine development.

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The emerging influenza virus threat: status and new prospects for its therapy and control

Cited by 78 publications

References 123 publications

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

Influenza A Virus Ribonucleoproteins Form Liquid Organelles at Endoplasmic Reticulum Exit Sites

Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials

<p>Immunoinformatics and Vaccine Development: An Overview</p>

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