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söndag 15 juli 2018

MicroRNA response in B-influenza

https://www.ncbi.nlm.nih.gov/pubmed/29766833

Microrna. 2018 May 14. doi: 10.2174/2211536607666180515111048. [Epub ahead of print]

Human MicroRNAs Expression Profiles in Influenza B Virus-Infected Cells based on Illumina MiSeq Platform.

Abstract

BACKGROUND:

Influenza B virus causes influenza-like illness in humans. MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression through mRNA degradation or translational repression. MiRNAs have evolved to regulate many cellular processes including the viral infection response.

OBJECTIVE:

This study aims to investigate the miRNA profiles of human cells infected with influenza B virus.

METHODS:

A549 cells were infected with influenza B viruses (MOI = 0.5). MiRNAs were extracted at 24 and 48 hours post-infection. MiRNAs were used to construct four DNA libraries: influenza B-infected and an uninfected control for both time points. Then high-throughput sequencing was performed using the Miseq platform (Illumina). Sequencing data were analyzed by Miseq reporter software. The miRNAs were categorized and counted based on the frequency of reads. All filtered contigs were aligned with data from miRbase. The relative expression of each miRNA between uninfected and influenza B-infected cells was calculated.

RESULTS:

There were 13 down-regulated miRNAs and 21 up-regulated miRNAs observed in influenza B infected cells at 24 hours post infection.
At 48 hours post infection, 14 miRNAs were down-regulated, whereas 8 miRNAs were up-regulated.

CONCLUSION:

This study suggested that miRNAs may play important roles in host gene regulation in response to viral infection.

KEYWORDS:

A549 cells; Miseq; expression profiling; influenza B virus; microRNAs; next-generation sequencing

Yhteenveto vuoden 2017-18 influenssasta tullut

https://www.google.com/search?client=firefox-b&q=Influensa+2018&spell=1&sa=X&ved=0ahUKEwjU6t2JnqHcAhUkCZoKHV-XCHYQBQgkKAA&biw=1024&bih=471&dpr=1.88
Sitaatti:

Influensarapport

Denna rapport publicerades den 12 juni 2018 och sammanfattar influensa-säsongen 2017-2018.
Influensaövervakningen avslutas nu för säsongen. Ett stort tack till alla som bidragit med data under säsongen. Trevlig sommar önskar vi som arbetat med influensarapporterna denna säsong!
Inför nästa säsong:
  • Den 1 oktober (vecka 40) börjar övervakningen igen.
  • Den 2 oktober anordnas Influensadagen, läs mer i kalendariet.
  • Influensavaccinationerna startar tisdagen den 6 november (vecka 45).

Sammanfattning

Influensasäsongen 2017–2018 dominerades av influensa B/Yamagata med en efterföljande våg av influensa A. Säsongens epidemi startade vecka 49 och nådde sin topp vecka 7. Totalt rapporterades 20 686 laboratorieverifierade influensafall, varav 65 procent var influensa B. Jämfört med de föregående säsongerna har betydligt fler influensafall rapporterats och antalet analyserade prover (totalt 88837 prov) har ökat främst från öppenvården. Snabbare och mer tillgänglig diagnostik har troligtvis bidragit till den stora ökningen. Även telefonsamtal till 1177 Vårdguiden och Webbsök visade på en intensiv säsong med många sjuka barn och vuxna. B/Yamagata är sedan tidigare känd för att främst drabba barn och unga vuxna när det cirkulerar i samhället men personer i dessa åldersgrupper klarar ofta av influensa hemma och behöver inte uppsöka sjukvård.
Att det ofta är yngre åldersgrupper som drabbas återspeglas inte i åldersfördelningen av de laboratorieverifierade fallen som består av personer som sökt vård. Åldersfördelningen bland de laboratorieverifierade fallen av influensa B visar att över hälften av fallen (55 procent) återfinns bland personer 65 år och äldre. Även sett till antalet fall per befolkningsmängd i respektive åldersgrupp (incidens) är personer 65 år och äldre hårdast drabbade av influensa B med en incidens på 359 fall per 100 000. Från vecka 12 och resterande veckor av säsongen skiftade dominansen från influensa B till A. Av de subtypade influensa A fallen var 65 procent A(H3N2). Även bland fallen av influensa A är det personer 65 år och äldre som drabbats i störst utsträckning med 58 procent av de laboratorieverifierade fallen. Antalet fall sett till befolkningsmängden är även högst i denna åldersgrupp med 211 fall per 100 000 invånare.
Medelvärdet för vaccinationstäckningen bland personer 65 år och äldre var 49 procent och har legat på samma nivå under de senaste säsongerna. Vaccinationstäckningen samlas in på olika sätt och små skillnader från år till år kan uppstå. Täckningsgraden är som högst bland personer 75 år och äldre (drygt 55 procent). Detta är positivt eftersom stigande ålder ökar risken för svår sjukdom vid influensainfektion. Det är stora variationer mellan landstingen/regionerna. Vaccinationstäckningen har ökat i nio landsting denna säsong. Bland personer under 65 år uppskattas att 5-10 procent tillhör en riskgrupp, men vaccinationstäckningen i denna åldersgrupp är endast 2 procent.
Antiviralt läkemedel för behandling av svår influensasjukdom samt profylax finns och försäljningsmönstret i Sverige följer laboratoriefallen. Denna säsong har antalet recept ökat med drygt 50 procent medan rekvisitioner från vården ökat med cirka 30 procent.
Under säsongen har 447 patienter rapporterats som intensivvårdade med influensa i hela landet och flera patienter har behövt ECMO vård jämfört med tidigare säsonger. Av de intensivvårdade patienterna hade majoriteten influensa B (288), medan 159 patienter hade influensa A. Av alla intensivvårdade patienter tillhörde 74 procent minst en medicinsk riskgrupp eller var 65 år och äldre. Bland patienter under 65 år tillhörde över hälften (116 patienter, 54 procent) inte en medicinsk riskgrupp. Åldersfördelningen bland intensivvårdade patienter under 65 år liknar säsongen 2015-2016, som dominerades av influensa A(H1N1)pdm09. Av de som tillhörde en riskgrupp och behövde intensivvård under denna säsong var endast 23 procent med känd vaccinationsstatus vaccinerade.
Denna säsong har en influensarelaterad överdödlighet uppmätts bland personer 65 år och äldre under perioden vecka 3 till 15. Överdödligheten motsvarar den för säsongen 2016-2017, då åldersgruppen 65 år och äldre drabbades hårt av influensa A(H3N2). Att en säsong som domineras av influensa B orsakar så hög överdödlighet är ovanligt eftersom influensa B inte brukar orsaka så stora epidemier, men det visar att äldre personer är de sköraste vad gäller risken att dö av influensa.
Bland personer som fått en laboratorieverifierade influensadiagnos hade 5,0 procent dött inom 30 dagar, vilket liknar föregående säsong då 5,6 procent hade avlidit. I analysen av de 1012 dödsfallen som skett inom 30 dagar var 93 procent av dödsfallen i åldersgruppen 65 år och äldre. Andelen fall som avlidit ökade med stigande ålder.
Viruskarakteriseringen av ett urval av de stammar som samlats in genom sentinelprovtagningen och från laboratorier i landet visar antigenisk likhet med vaccinstammen för A(H1N1)pdm09. Majoriteten av A(H3N2)- stammarna hade antigenisk likhet med cell-odlad men sämre likhet för ägg-odlad vaccinstam. B/Yamagata-stammarna tillhörde genetisk grupp som är antigeniskt lik vaccinstammen i det fyrvalenta vaccinet (ingår ej i det trivalenta vaccinet). Endast en stam av 343 analyserade var resistent för oseltamivir (ej för zanamivir)
Inom sentinelprovtagning var merparten av proverna B/Yamagata (76,9 procent) följt av 16,5 procent A(H3N2) och 5,4 procent A(H1N1)pdm09. Folkhälsomyndigheten deltar i det europeiska nätverket för att mäta influensavaccinets effekt (I-MOVE) med data från den svenska sentinelprovtagningen. Vid interimsrapporten för säsong 2017-2018 var vaccinationseffekten för A(H1N1)pdm09 god (55-68 procent), för B måttlig (36-54 procent) och för A(H3N2) låg (<7 procent). Detta visade att B/Victoria i det trivalenta säsongsinfluensavaccinet gav korsskydd mot B/Yamagata, den linjetyp som cirkulerade under säsongen.
Antal laboratorieverifierade influensafall (alla typer) per vecka, denna säsong och tidigare säsonger.
Graf som visar antalet laboratorieverifierade fall av influensa i Sverige under de senaste 5 säsongerna, från 2013-2014 till 2017-2018.

Länkar

Folkhälsomyndighetens sjukdomsinformation om influensa
Folkhälsomyndighetens information om influensavacciner
WHO & ECDC:s influensarapport (FluNewsEurope) (publiceras varje vecka)
WHO:s influensarapport (publiceras varannan vecka)
European monitoring of excess mortality for public health action (EuroMOMO)

onsdag 4 juli 2018

Koottua tietoa netistä rinoviruksesta

Kysymyksiä, joihin etsin vastausta: Mikä on  ihmiskehon vaste rinovirukseen ja miten jokin rhinovirus kiertää ihmisen immuunivasteen?
Mitkä ovat tyypillisimmät erot  influensaviruksesta tuleviin oireisiin?
saako rinoviruksiin vasdtustuskykyä?
Onko rokotettta ja onko rokoteen tarvetta?
Mikä on pahin haitta tai vaara  rinoviruksista aikuisille? lapsille?

Materiaalia, jota löysin tänään
 
Challenges in developing a cross-serotype rhinovirus vaccine. Glanville N et al. Curr Opin Virol. (2015) Abstract
 A great burden of disease is attributable to human rhinovirus (HRV) infections which are the major cause of the common cold, exacerbations of both asthma and chronic obstructive pulmonary disease (COPD), and are associated with asthma development.
 Despite this there is currently no vaccine for HRV.
 The first vaccine studies showed some promise in terms of serotype-specific protection against cold symptoms, but antigenic heterogeneity amongst the >150 HRVs has been regarded as a major barrier to effective vaccine development and has resulted in little progress over 50 years.
 Here we review those vaccine studies conducted to date, discuss the difficulties posed by antigenic heterogeneity and describe some recent advances in generating cross-reactive antibodies and T cell responses using peptide immunogens.

(Siis toistaiseksi: olennaista saada PEF arvot tulehduksen jälkeen vähintään samalle tasolle kuin ennen tulehdusta, restriktio ei saa jäädä ja kestää ja pinttyä- ehkä  lyhytaikainen tukea antava  astmaattisia keuhkomuutoksia estävä    ehkä steroidipitoinen inhalaatio hoito olisi astmaprofylaksian kannalta   suositeltava rhonoviruksesta toipumisen jälkeen, ja keuhkorestriktio asteen  kontrolli, palautttaminen ainakin ennen tulehdusta esiintyneisiin keuhkofunktiotasoihin - tässä on sokea piste terapeuttissti ajatellen. Jokainen  paha rhinovirusinfektio voi tuhota joitain funktionaalisia soluja9

 
The potential for a protective vaccine for rhinovirus infections. Williams GR et al. Expert Rev Vaccines. (2016)
Rhinovirus A , B and C, 7 subtypes (A(4), B(1), C (2) . Intraspecies recombinations in A and C.


Kommentti: Rhinovirus on tavallinen ssRNA virus, jolle kehossa on ssRNA sensori RIG-1, adaptori MAVS, joiden kauta  tapahtuu  INF tyyppi1 – antiviraalin vasteen indusoivan  interferonin tuotanto .

  • PubMed artikkeli vuodelta 2017. C-tyypin Rhinoviruksen evaasiostrategiasta.
Rhinovirus tyyppi C: stä enemmän tekstiä , sillä se kiertää jollain tavalla tämän RIG-1 välitteisen tunnistustien. (tunnistus tarkoittaa: Solu huomaa että sisään on tullut vieras RNA- materia. Jos se on lyhyst ssRNA, RIG-1 tunnistaa sen. Sitten on RIG-1 :n kaltaisia reseptoreita muitakin joilla voidaan laajentaa tunnistettavien  RNA virusten  valikoimaa.

 Tutkijat kehittivät RV-C viruksen kliinisistä näyteistä kokopitkän cDNA-kloonin. RV-C ei nostanut IFNbeta mRNA eikä -proteiinitasoja bronkiaaliepiteelin infektoiduissa soluissa. Tämä kyky heikentää IFNbeta aktivaatio havaittiin olevan RV-C- viruksen 3C-proteiinilla, jossa eräs histidiini (40H) oli tärkeässä asemassa. Tämä proteiini 3C aiheutti RIG-1 sensorin hajoamisen kaspaasista riippuvalla tavalla ja virusproteiini pystyi myös pilkkomaan adaptorin  MAVS  kohdasta 148 Q/A, mikä lopullisesti esti IFN-1--signaloinistien. Yhteenvetona RV-C pystyi suorittamaan evaasionsa ylläkuvatulla mekanismilla siten, että infektoitunut solu ei tuottanut IFN-I tyypin interferonia ( eikä siis solu saanut sen avulla normaalia antivirustilaasa aikaan, jolloin olisi yli sata antivirusgeeniä ollut valittavana käynnistettäväksi).

(Käytännön emrkitys:
 Rhinoviruksenkin tyypin diagnosoiminen saattaa olla tärkeä asia. Rokotteesta olisi hyötyä astmaan taipuvaisille, sillä jokainen pahanlaatuinen Rhinovirus vikuuttaa keuhkoa. Ehkä keskittyminen influenssavirustieteeseen on ottanut kaikki reseurssit maailmasta ja rhinovirus on jäänyt sen varjoon- vaikka käytännössä jälkitauti astma  ja pahentunut COPD on hankalampi kuin influenssan usein  olemattomat jälkitaudit  ja lisäksi influenssa jättää jotain immuunivastetta. 

  • Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling.
  •  Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.KEYWORDS: 3C protein; Interferon response; MAVS; RIG-I signaling pathway; Rhinovirus C. PMID: 28576493 DOI: 10.1016/j.bbrc.2017.05.169 [Indexed for MEDLINE]
  • Tietoa vuodelta 2006. Yli 100 rinovirusta tunnetu siihen aikaan. Noin 50 % tavallisista vilustumisista aiheutui jostain rinoviruksesta.
Tak W. Mak, Mary E. Saunders, in The Immune Response, 2006
  • Rhinovirus.

  • Rhinovirus (rhino, “nose”) is a non-enveloped, single-stranded RNA virus and a member of the picornavirus family. Over 100 rhinoviruses are known. About 50% of common colds are caused by some kind of rhinovirus. (About 10% of common colds are due to infection with a different type of virus, such as adenovirus, while the cause in 40% of cases is unknown.)
  • Rhinoviruses thrive in the upper respiratory tract, particularly the nose and throat. The infection is thus characterized by the familiar symptoms of sneezing, excessive nasal secretion (“runny nose”), and congestion (“stuffy nose”). Complications of rhinovirus infection include spreading of the virus from the throat to the sinuses, lower respiratory tract, and middle ear, resulting in sinusitis, laryngitis, and otitis media, respectively.
Löydän valmiin luettelon isäntäkehon vasteesta rhinovirukselle:
  • Host Immune Response To Rhinovirus

  1. 1. Narissara Suratannon, MD. Copyright © Wondershare Software
  2. 2. Introduction 50% of children undergo viral respiratory tract infections cause wheezing illnesses RSV, HRV and mixed viral infections are the most common causes RSV : December to April (Thai : May to July) HRV : the rest of the year 30-50% with recurrent virus-induced wheezing in infancy go on to develop asthma Gern et al.JACI2006;117:72-8 James E. Gern.Curr Opin in aller Wondershare Software Copyright © and Imm.2009:9:73-8
  3. 3. Introduction The question of whether respiratory infections with viruses can cause asthma is controversial Infections with RSV : subsequent increased risk of recurrent wheezing and asthma (Lancet 1999) Molecular studies have showed the role of HRVs to acute illness and in exacerbations of asthma and COPD James E. Gern.Curr Opin in aller Wondershare Software Copyright © and Imm.2009:9:73-8
  4. 4. Outline How rhinovirus attack our body? How our body responses it? Do viruses increase the risk of developing subsequent wheezing and asthma? Role of virus for acute asthma exacerbation Rhinovirus as a predictor of severity of asthma Copyright © Wondershare Software
  5. 5. Rhinovirus is an important respiratory pathogen • Most common pathogen – half of all colds – >100 infections in a lifetime - founds everywhere • URI – including middle ear and sinuses • LRI – “At risk” populations (infants, elderly, COPD, CF) – Bronchiolitis, bronchitis, pneumonia • Asthma: exacerbation (and causation?) Some part from Dr.Gern’s Slide Copyright © Wondershare Software
  6. 6. What is HRV (Human Rhinovirus)? First recovered in 1950s Rhino = nose small nonenveloped viruses contain a single-strand RNA Family : Picornaviridae Species : Enterovirus Genus : Rhinovirus James E. Gern.Curr Opin in aller and Imm.2009:9:73-8 Copyright © Wondershare Software Pic. from Wigepidia
  7. 7. Structures of Rhinovirus Capsid (VP1,2,3) : antigenic diversity Central RNA core (VP4-located inside) Divided on... basis of susceptibility to antiviral agents into HRV-A , HRV-B , new groups: HRV “C” Receptors binded to ECs into major and minor groups Copyright © Wondershare Software James E. Gern.Curr Opin in aller and Imm.2009:9:73-8 Pic. from Wigepidia
  8. 8. Why Rhinovirus come in our interesting? Hospitalizd asthmatic patients correlate with the seasonal peak of rhinovirus Recent observations found that rhinovirus could present in the lower airway and in parenchyma Korppi et al.- Bronchiolitic children (RSV & HRV) Pediatr Infect Dis J 2004;23:995-9 Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  9. 9. Clinical evidences for viral induced.. Subsequent wheezing (1) Subsequent asthma (2) Copyright © Wondershare Software
  10. 10. Lemanske et © Wondershare Software Copyright al.JACI 2005;116:571-7
  11. 11. Lemanske et © Wondershare Software Copyright al.JACI 2005;116:571-7
  12. 12. Non-viral factors Lemanske et © Wondershare Software Copyright al.JACI 2005;116:571-7
  13. 13. Viral factors Lemanske et © Wondershare Software Copyright al.JACI 2005;116:571-7
  14. 14. First year wheezing caused by rhinovirus infections were the strongest predictors of subsequent third year wheezing Lemanske et © Wondershare Software Copyright al.JACI 2005;116:571-7
  15. 15. Targets for Infection Epithelium is the primary target site of HRV!! CopyrightBusse.JACI 2008;122:671-82 Kelly and © Wondershare Software
  16. 16. host-cell recognition of dsRNA seems to be an important pathway for the initiation of multiple pro-inflammatory and antiviral pathways Abul K. Abbas et al.,Cellular and Molecular Immunology,6th ed,2007,p.23 Copyright © Wondershare Software
  17. 17. Kallal et al. Current Allergy and Asthma Reports 2008, 8:Software Copyright © Wondershare 443– 450
  18. 18. Epithelium Rhinovirus-infected ECs produced cytokines and chemokines for recruitment of inflammatory cells as a host viral immune response IL-1, IL-6, IL-8, GM-CSF, eotaxins, and RANTES, type I IFN Target of the virus Reservoir for the infected virus The site and source of initial inflammatory response Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  19. 19. How our body response to HRV? Innate immune response Macrophages Neutrophils Eosinophils Adaptive immune response T-cells B-cells Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  20. 20. Kelly Copyright © Wondershare Software and Busse.JACI 2008;122:671-82
  21. 21. Macrophages Rhinovirus can attach to macrophages but may have limited replication This interaction stimulates secretion of IL-1, IL-8, TNF-α, IFN- α TNF-α induction of EC expression of ICAM-1 Allows for leukocytes trafficking Increases the receptor availability on the cells IL-8 : potent chemokine for neutrophil IFN- α : limit virus spread by an antiviral state in ECs (strengthen anti-viral responses) Kelly Copyright © Wondershare Software and Busse.JACI 2008;122:671-82
  22. 22. Type 1 IFN (α and ß) Induced “antiviral state” Inhibit viral replication induce cells to synthesize enz. that interfere viral replication .Protect neighboring cells (paracrine action) Increases expression of MHC class 1 and development of TH1 cells Regulate apoptosis of infected cells Abul K. Abbas et al.,Cellular and Molecular Immunology,6th ed,2007,p.23 Copyright © Wondershare Software
  23. 23. Neutrophils predominant cell type in both asthma and control subjects Peripheral blood neutrophils increase Correlate with rising of G-CSF and IL-8 levels Neutrophil elastase : a marker of neutrophil degranulation Benefit or harmful? Clearance of cellular debris via phagocytosis Airway edema , trigger bronchoconstriction and induce mucous gland secretion from goblet cells Kelly Copyright © Wondershare Software and Busse.JACI 2008;122:671-82
  24. 24. Eosinophils - Increases in both asthma and control subjects (Holgate et al. 1995) - EDN , ECP : antiviral properties (Rosenberg. J 2001) - Expressed ICAM-1 when pretreated with GM-CSF - Eosinophils may act as APC : expressed MHC II , CD 40L when pretreated with IFN-Ɣ, GM-CSF,TNF-α Handsel and Copyright © Wondershare Software Busse.J Immunol 1998;160: 1279–84
  25. 25. Eosinophils Only in asthma subjects does the eosinophilic infiltrate persist 6 to 8 weeks after infection Correlate with airway hyperresponsiveness Reflected by increase ECP, leukotrienes Increased sputum eosinophils predict loss of asthma control Barns et al.AJRCCM 2000;161:64–72 Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  26. 26. Adaptive Immune Response T-cell (intracellular phase) Infected ECs secrete RANTES and IP-10 for promote T-cell chemotaxis Expression of IP-10 required active rhinovirus replication TH1-cytokines (IL-2, IFN-Ɣ) CTLs and NKT cells B- cell (extracellular phase) Neutralizing Abs Opsonization Kelly Copyright © Wondershare Software and Busse.JACI 2008;122:671-82
  27. 27. Effective antiviral activity vs Damaging inflammation Highly variable among individuals Determines whether the patients wheeze or has a rapid resolution of the viral illness Gern and Busse. Nat Rev Imm.2002 Software Copyright © Wondershare ;2:132-9
  28. 28. Risk factors for virus-induced wheezing Young age (< 6 months) Small lung size (Ped Resp Rev 2004) Exposure to tobacco smoke Pre-existing airway hyperresponsiveness Several genetic factors polymorphisms in genes encoding surfactant proteins, cytokines and chemokines (RSV) HRV – polymorphims in IL-10 ?? Helminen et al. Pediatr Pulmonol 2008;43:391-5 James E. Gern.Curr Opin in aller Wondershare Software Copyright © and Imm.2009:9:73-8
  29. 29. Clinical evidences for viral induced.. Subsequent wheezing (1) Subsequent asthma (2) Copyright © Wondershare Software
  30. 30. Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  31. 31. Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  32. 32. Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  33. 33. Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  34. 34. Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  35. 35. Non-viral factors Copyright © Wondershare Software Jackson et al.Am J Respir Crit Care Med 2008;178:667-72
  36. 36. Clinical studies show relationship between RSV/RV- induced wheezing and subsequent asthma But the nature of this association has not yet been clearly defined Gern and Busse. Nat Rev Imm.2002 Software Copyright © Wondershare ;2:132-9
  37. 37. 2-Hit Hypothesis Lemonske. Ped AI 2002: Wondershare Software Copyright © 13 (Suppl. 15): 38–43
  38. 38. More virulent ?? Copyright © Wondershare Software
  39. 39. What determines the severity of rhinovirus respiratory illnesses? Copyright © Wondershare Software
  40. 40. Host Factors Critical period of lung development Atopy Impaired IFN production Allergen sensitization Epithelial defect (barrier defect) : filagrrin Copyright © Wondershare Software Holgate JACI 2006;118:587-90
  41. 41. James E. Gern.Curr Opin in aller Wondershare Software Copyright © and Imm.2009:9:73-8
  42. 42. Multivariate analysis (Gender, older siblings, environmental tobacco smoke exposure, breast feeding, daycare attendance, parental asthma) Copyright © Wondershare Software Kusel et al.JACI 2007;119:1105-10
  43. 43. Reijonen et al.Pediatrics© Wondershare Software Copyright 2000; 106(6); 1406-10
  44. 44. Copyright © Wondershare Software
  45. 45. Cofactors that may contribute to asthma Air pollution: personal NO2 exposure – Chauhan A, Lancet 361:1939, 2003 Tobacco smoke, non-use of ICS – Venarske, JID 193:1536, 2006 Copyright © Wondershare Software James E. Gern.Curr Opin in aller and Imm.2009:9:73-8
  46. 46. In the case of increased epithelial permeability (diseased airways) RV infection is more severe !! Copyright © Wondershare Software James E. Gern.Curr Opin in aller and Imm.2009:9:73-8
  47. 47. Copyright © Wondershare Software From Dr. Gern’s slide
  48. 48. Asthma and Viral Respiratory Infections Most asthma exacerbations (50-85%) are related to viral infection Any respiratory pathogen (eg, RSV, parainfluenza) can precipitate attacks, but RV are the most common Seasonal VRIs correlate with hospital admissions for asthma Johnston SL, et al. BMJ. 1995;310:1225–9 Copyright © Wondershare Software Johnston SL, et al. AJRCCM. 1996;154:654-60
  49. 49. Why are some patients with asthma more susceptible to rhinovirus LRI? Not all asthmatic patients have an exacerbation with a cold Some patients - impaired anti-viral response Enhanced of rhinovirus replication Causing greater airway inflammation acute exacerbation A reduction of IFN-Ɣ/IL-5 mRNA ratios from sputum of asthma subjects correlate with higher symptom scores TH2 cytokines induce ICAM-1 expression on ECs Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  50. 50. Persistence of Rhinovirus to be a predictor of asthma severity Some subjects of asthma show the presence of rhinovirus without cold symptoms or exacerbation Correlated with a greater degree of airflow obstruction Whether rhinovirus infection can become persistent and contribute to asthma severity has yet to be established Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82
  51. 51. Summerization Asthma is probably a heterogeneous disease 3 factors that significantly influence asthma inception in the first decade of life immune response aberrations : concept of cytokine dysregulation (TH1/TH2 imbalance) LRTIs in particular RV gene–environment interaction (needs to occur at a critical time-period in the development of the lung) Lemonske. Ped AI 2002: Wondershare Software Copyright © 13 (Suppl. 15): 38–43
  52. 52. Summerization Children who wheeze with HRV may be at particularly high risk for the subsequent development of asthma The relationship between respiratory infections and induction of asthma is complex : interactions between host factors such as age and stage of development of innate and adaptive immune mechanisms at the time of infection (immune maturation) pathogenic factors such as the number and severity of infections Copyright © Wondershare Software
  53. 53. Summerization New approach to asthma prevention and treatment , try to protect airways against environmental insults rather than focusing on the suppression of inflammation Copyright © Wondershare Software
  54. 54. Rhinovirus equally infects upper and lower airways was previously thought to infect primarily upper airway epithelium (Optimal replication occurs between 33 and 35 °C) Has been detected in lower airway ECs and secretions after experimental inoculation with rhinovirus (BT 37 °C) Mosser et al. Am J Respir Crit Care Med 2005; 171:645–51 Copyright © Wondershare Software Kelly and Busse.JACI 2008;122:671-82


Vilustumisvirus, Fökylningsvirus

http://www.doktorn.com/artikel/skillnaden-p%C3%A5-f%C3%B6rkylning-och-influensa-s%C3%A5-undviker-du-att-bli-sjuk

Rinovirus (rhinovirus) on eräs tavllisten vilustumisvirusten ryhmä

Rinovirus (THL lähteestä)


Mikä on rinovirus?

Rinovirukset kuuluvat pikornaviruksiin. Niistä tunnetaan yli 150 virustyyppiä, jotka jaetaan A-, B- ja C-lajiin.
Rinovirukset ovat yleisimpiä flunssan eli nuhakuumeen aiheuttajia. Rinovirusinfektioita esiintyy erityisesti kevättalvisin ja syksyisin.

Miten rinovirus tarttuu?

Rinovirusinfektio tarttuu helposti käsien välityksellä. Virusta siirtyy hengitystie-eritteistä käsiin ja käsistä toisiin ihmisiin ja edelleen käsien kautta suun tai nenän limakalvolle. Myös pisaratartunta hengitystie-eritteiden kautta on mahdollinen.

Mitkä ovat rinovirusinfektion oireet?

Suuri osa rinovirusten aiheuttamista infektioista on oireettomia tai hyvin vähäoireisia. Infektiot ovat yleisimpiä pienillä lapsilla, mutta niitä voi esiintyä kaikenikäisillä.
Rinovirus aiheuttaa yleensä ylempien hengitysteiden infektion, jonka oireita ovat nuha, kurkkukipu, ja mahdollisesti lämpöily. Joskus rinovirusinfektio johtaa välikorvantulehdukseen tai poskiontelotulehdukseen. Rinovirus voi liittyä myös alempien hengitysteiden infektioihin, kuten keuhkokuumeeseen tai bronkioliittiin.

Miten rinovirustartunta todetaan?

Rinovirustartunta voidaan todeta osoittamalla virus nenänielulimasta esim. geeninmonistusmenetelmällä.

Miten rinovirusinfektioita hoidetaan?

Rinovirusinfektioon ei ole lääkitystä vaan hoito on oireenmukaista.

Miten rinovirusinfektioita ehkäistään?

Rinovirusinfektioita vastaan ei ole rokotusta.
Tartunnan leviämistä estää huolellinen käsihygienia. Kädet pestään runsaalla vedellä ja pesunesteellä/saippualla erityisesti ennen ruokailua. Käsienpesu on tärkeää myös kun on kohdattu flunssaa sairastavia ihmisiä ja käsitelty yhteisiä tavaroita.

måndag 21 maj 2018

ESCRT-0 HRS omaa FYVE- PI-3-K motiivin .olisiko tässä kohta, johon on anti EBOV-lääke, Apilimod

 EBOV tarvitsee ehdottomasti  korkeampien organismien fosfoinositidilipidilaatuja virionin valmistukseen.  ja ilmeisesti muihinkin  vaiheisiin. 

Abstract
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM). We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication. After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV. Concurrently apilimod caused VLPs to accumulate in early endosome antigen 1-positive endosomes. We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm. Given the drug’s observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.

The Phosphatidylinositol-3-phosphate... (PDF Download Available). Available from: https://www.researchgate.net/publication/316078827_The_Phosphatidylinositol-3-phosphate_5-kinase_inhibitor_Apilimod_blocks_filoviral_entry_and_infection?_sg=jHD1ro2wp8OvvZ9-i_RrU8KdUSjG5m95aksJdi4LV3XOz-A4q8nBzgYUjn6qoD1H02-d45KZOdtfy1ITq6T3aZSqqTtfOCKNlg [accessed May 21 2018].
Abstract
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV).

We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM).

We next observed that similar doses of apilimod block EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication competent VLP infection, suggesting that the primary mode of action of apilimod is as an entry inhibitor, preventing release of the viral genome into the cytoplasm to initiate replication.

After providing evidence that the anti-EBOV action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular receptor for EBOV.

Concurrently apilimod caused VLPs to accumulate in early endosome antigen 1-positive endosomes.

We did not detect any effects of apilimod on bulk endosome acidification, on the activity of cathepsins B and L, or on cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod appears to block EBOV trafficking to its site of fusion and entry into the cytoplasm.

Given the drug’s observed anti-filoviral activity, relatively unexplored mechanism of entry inhibition, and reported tolerability in humans, we propose that apilimod be further explored as part of a therapeutic regimen to treat filoviral infections.

The Phosphatidylinositol-3-phosphate... (PDF Download Available). Available from: https://www.researchgate.net/publication/316078827_The_Phosphatidylinositol-3-phosphate_5-kinase_inhibitor_Apilimod_blocks_filoviral_entry_and_infection?_sg=jHD1ro2wp8OvvZ9-i_RrU8KdUSjG5m95aksJdi4LV3XOz-A4q8nBzgYUjn6qoD1H02-d45KZOdtfy1ITq6T3aZSqqTtfOCKNlg [accessed May 21 2018].

Kts. ESCRT complex:  endosomaalisessa kalvosaa PIP3 ja ESCRT-0  kompleksin jäsen    Hrs, jolla on  FYVE- domeeni, joka kiinnittyy PI3P molekyyliin.
Bildresultat för hrs/vps27, ESCRT-0

https://openi.nlm.nih.gov/detailedresult.php?img=PMC2172707_200302136f7&req=4








Kongon Ebola, Mortaliteetti 56%, 26 kuollutta, näistä kolme terveysalan työntekijää; 45 varmaa tapausta

http://www.who.int/news-room/detail/18-05-2018-statement-on-the-1st-meeting-of-the-ihr-emergency-committee-regarding-the-ebola-outbreak-in-2018