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onsdag 29 juni 2022

Apuluettelo linjojen definioivien mutaatioiden löytämiseen

 https://www.pango.network/summary-of-designated-omicron-lineages/

Päivä vierähti kun etsin tietoa sars-2 Cov ORf7b virusproteiinin funktioista ja rakenteesta.

 https://www.frontiersin.org/articles/10.3389/fmicb.2021.654709/full

Asetanjonkin  linkin jo  esiin tähän blogiin.  

Pitää myös tarkistaa, missä kaikissa varianteissa esiintyy Orf7b muutoksia ja mikä oli  Orf7b alkuperäinen funktio. Sars-1ja sars-2 virusten  Orf7b omaa noin 81%:sta   samankaltaisuutta.

ORF7b mutaatiosta L11F ja frameshift- ilmiöstä S: R346T substituutioon ja 8nt deletioon liittyneenä.

 

Katsoin tänään Orf7b proteiinirakenteen ( sekvenssin). Siinä on 43 aminohappoa Swissmodel kuvassa.

Orf7b merkityksestä on artikkeli  viime vuoden elokuulta. Nyt huomasin GITHUB uutisista,  että BA.4 variantti tekee alalinjoja ja niissä esiintyy mutaatio Orf7b:sä  L11F. Se on proteiinin transmembraanista (TM) aluetta (9-29 aminohapot käsittävä jakso)

Nyt on alkanut esiintyä spike-mutaatiota eri linjoissa: R346T, joilla on kasvuetua. Tähän mutaatioon liittyy  - ehkä konsekventisti?-  8nt deletio ORF7b:ssä ja siitä seura iso frameshift-ilmiö, joka aiheuttaa miltei koko transmembraanisen (TM)jakson tilalle 18 aivan uuden aminohaponsekvenssin j  ja typistää loppuproteiinin sen jälkeen, joten Orf7b proteiini lyhenee samalla 43 aminohaposta vain 29 aminohappoa käsittäväksi.

Katsoin Swiss modellin selittämän peptidisekvenssin. Teen sitten uuden peptidin kaavan sen alle tästä GITHUB-selvityksestä /#741). 

 Swissmodell ei tarjonnut Orf7b proteiinille hahmomallia.

 Trasnmembraanijakso (9 FY LCFLAFLLFL VLIMLIIFW 29) tummennettuna


Orf7bWuhan sekvenssi:

1 MIELSLIDFY LCFLAFLLFL VLIMLIIFWF SLELQDHNET CHA 43

Orf7b omaa mutaation BA.4 linjassa: 11 asemassa : L11F.

Spikemutaatioon R346T assosioituu  Orf7b 8nt deletio, luennan muutos ja aivan uuden aminohappojakson asetus Orf7b peptiidiin sen asemasta 10  ja sitten loppuosan päättäminen siihen uuden jakson päätyyn, joten tulos lie seuraava: Uudet aminohapot vinolla kirjoituksella ja viiva alla.

1 MIELSLIDFY FSLSVIPCFN YAYYLLVLT (En ole varma jos FY jotka ovat 9 ja 10 asemassa ovat säilyneet siten että Y ei poistu kun L11F tapahtuu).



2021 Aug 13;12:654709.

doi: 10.3389/fmicb.2021.654709. eCollection 2021.

SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-α-Induced Apoptosis in Cells

Ruiping Yang  1   2 Qiong Zhao  1 Jingjing Rao  1 Feng Zeng  1 Shengren Yuan  1 Manshan Ji  1 Xiaoguang Sun  1 Jian Li  1 Jing Yang  1   2 Jingwen Cui  1 Zhixiong Jin  1   3 Long Liu  1   2   3 Zhixin Liu  1   2   3

Affiliations

Free PMC article Abstract

The accessory proteins of coronaviruses are essential for virus-host interactions and the modulation of host immune responses. It has been reported that accessory protein ORF3a encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce apoptosis, and accessory protein ORF6 and ORF8 could be inhibitors of the type-I interferon (IFN) signaling pathway. However, the function of accessory protein ORF7b is largely unknown. We investigated the apoptosis-inducing activity of ORF7b in cells. Cytokine levels and host innate immune responses, including expression of interferon regulatory transcription factor (IRF)-3, signal transducer and activator of transcription (STAT)-1, interferon (IFN)-β, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were also investigated. We found that ORF7b promoted expression of IFN-β, TNF-α, and IL-6, activated type-I IFN signaling through IRF3 phosphorylation, and activated TNFα-induced apoptosis in HEK293T cells and Vero E6 cells. These results could provide deeper understanding about the pathogenicity of SARS-CoV-2 as well as the interaction between the accessory protein ORF7b with host immune responses.

Keywords: ORF7b; SARS-CoV-2; apoptosis; immune responses; interferon.

Copyright © 2021 Yang, Zhao, Rao, Zeng, Yuan, Ji, Sun, Li, Yang, Cui, Jin, Liu and Liu.


tisdag 28 juni 2022

Mikä aiheuttaa omikron varianttien tavatonta mutaatiopaljoutta?

Asiaa on pohdittu tieteellisissä artikkeleissa:
Review
. 2022 Jun 24;1-9.
doi: 10.1007/s11357-022-00603-6. Online ahead of print.

SARS-CoV-2 infection in HIV-infected patients: potential role in the high mutational load of the Omicron variant emerging in South Africa

Affiliations
Free PMC article
Abstract

A new variant of SARS-CoV-2 named Omicron (B.1.1.529) was isolated from an HIV-infected patient in Botswana, South Africa, in November 2021. Whole genome sequencing revealed a multitude of mutations and its relationship to the mutation-rich Alpha variant that had been isolated from a cancer patient. It is conceivable that very high prevalence of HIV-infected individuals as susceptible hosts in South Africa and their immunocompromised state may predispose for accumulation of coronavirus mutations. Coronaviruses uniquely code for an N-terminal 3' to 5'exonuclease (ExoN, nsp14) that removes mismatched nucleotides paired by the RNA dependent RNA polymerase. Its activity depends preferably on Mg2+ and other divalent cations (manganese, cobalt and zinc). On the contrary, methyl transferase activity of non-structural protein (nsp) 14 and nsp16 both complexed with nsp10 requires Mn2+. Enzymes in successive stages of HIV infections require the same cations. In HIV-infected organisms, a subsequent coronavirus infection encounters with altered homeostasis of the body including relative starvation of divalent cations induced by interleukin production of HIV-infected cells. It is hypothesized that selective diminished efficacy of ExoN in the absence of sufficient amount of magnesium may result in the accumulation of mutations. Unusual mutations and recombinations of heterologous viruses detected in AIDS patients also suggest that long-lasting persistence of superinfecting viruses may also contribute to the selection of genetic variants. Non-nucleoside reverse transcriptase inhibitors partially restore divalent cations' equilibrium. As a practical approach, implementation of highly active antiretroviral therapy against HIV replication and vaccination against coronaviruses may be a successful strategy to reduce the risk of selection of similar mutants.

Keywords: Coronavirus; Divalent cations; Exonuclease; Human immunodeficiency virus; Interaction; Variant Omicron.

Omikronrekombinantteja tullut edelleen lisää PANGO-listaan: XAD, XAE, XAF, XAG, XAH

 Viimeisimmät  omikronien rekobinanttilisät PANGOlistassa: 

XAD

420Recombinant lineage of BA.2 and BA.1, Germany lineage, from pango-designation issue #607
XAE

60 0 Recombinant lineage of BA.2 and BA.1, USA and Chile lineage, from pango-designation issue #637
XAF

71 0 Recombinant lineage of BA.1 and BA.2, Costa Rica lineage, from pango-designation issue #676
XAG

47 0 Recombinant lineage of BA.1 and BA.2, lineage in Brazil and other countries, from pango-designation issue #709
XAH

58 0 Recombinant lineage of BA.2 and BA.1, lineage in Slovenia and other countries, from pango-designation issue #755

BA.4 variantti ja sen alalinjat 28.6. 2022

Lineage Most common countries Earliest date # designated # assigned Description WHO Name
BA.4 United States of America 29.0%, South_Africa 16.0%, United Kingdom 16.0%, Israel 8.0%, Germany 6.0% 2022-01-10 448 15762 Alias of B.1.1.529.4, from pango-designation issue #517 Omicron
BA.4.1

564 0 Alias of B.1.1.529.4.1, mainly found in South Africa, from pango-designation issue #548
BA.4.1.1

49 0 Alias of B.1.1.529.4.1.1, mainly found in South Africa and Germany, from pango-designation issue #667
BA.4.1.2

91 0 Alias of B.1.1.529.4.1.2, Austria lineage
BA.4.1.3

34 0 Alias of B.1.1.529.4.1.3, Israel lineage
BA.4.1.4

54 0 Alias of B.1.1.529.4.1.4, Israel lineage
BA.4.2

277 0 Alias of B.1.1.529.4.2, USA lineage
BA.4.3

53 0 Alias of B.1.1.529.4.3, Israel lineage
BA.4.4

552 0 Alias of B.1.1.529.4.4, USA lineage
BA.4.5

34 0 Alias of B.1.1.529.4.5, Australia lineage

 

måndag 27 juni 2022

Israelin covid-19-pandemiatilanne tällä viikolla 27.6. 2022

 

The Health & Wellness portal is presented in collaboration with

COVID-19 in Israel: 6,267 new infections, serious cases continue to rise

Since the start of the COVID-19 pandemic in March 2020, Israel has recorded 10,926 coronavirus-related deaths, 16 of which occurred in the last seven days.


An undated transmission electron micrograph of SARS-CoV-2 virus particles, also known as novel coronavirus, the virus which causes COVID-19, isolated from a patient.
(photo credit: NIAID INTEGRATED RESEARCH FACILITY (IRF)/HANDOUT VIA REUTERS)

A total of 6,267 new COVID-19 infections were recorded across Israel on Saturday bringing the total number of active cases in the country to 54,603, according to a Sunday morning Health Ministry update.

Of that number, 255 people are considered to be in serious condition, with 41 of them intubated and another two people connected to ECMO machines. There was a 41.54% positive return rate for some 15,000 PCR and antigen tests taken throughout the day on Saturday.

The R-rate currently stands at 1.22, continuing a downward trend that has been seen in recent days. However, even though the number does seem to be dropping, there is still cause for concern as it is still considerably above 1 and therefore the disease is continuing to spread at an increased rate.

Recent infections 

While the overall number of new COVID-19 infections recorded on Saturday is lower than in previous days, when over 10,000 new cases were reported multiple days in a row, this is to be expected as testing is always much lower over the weekend.

Additionally, compared to prior weekends in the month of June, the 6,267 new cases are considerably more than reported previously. For example, on Saturday, June 18 there were 4,971 new cases and on Saturday, June 11 there were just 3,338 new cases. 

 Shaare Zedek hospital team members wearing safety gear as they work in the Coronavirus ward of Shaare Zedek hospital in Jerusalem on February 09, 2022. (credit: OLIVIER FITOUSSI/FLASH90)

Since the start of the COVID-19 pandemic in March 2020, Israel has recorded 10,926 coronavirus-related deaths, 16 of which occurred in the last seven days.

USA:n ensimmäinen A H5N1 influenssan ihmisinfektiotapaus tänä vuonna

Avian Influenza A (H5N1) - United States of America

6 May 2022

Situation at a glance:

WHO was notified of a human case of avian influenza A (H5) in Colorado State in the United States of America on 29 April 2022.  The case was involved in culling of poultry at a farm where influenza A (H5N1) virus was confirmed in the poultry. Avian influenza A (H5) was confirmed in the case on 27 April by the US Centers for Disease Control and Prevention and subtype N1 was confirmed subsequently by sequence analysis. The close contacts and people involved in culling of poultry have been identified, tested and are currently being followed up. Based on available information, WHO assesses the risk to the general population posed by this virus to be low and for occupationally exposed persons it is considered to be low-to-moderate. 

This is the first human case of influenza A (H5N1) virus reported in the United States of America.  

Description of the case:

On 29 April 2022, the National IHR Focal Point of the United States of America notified WHO of a laboratory confirmed human case of avian influenza A(H5), in a male from Colorado State.

The case developed fatigue on 20 April, during participation in slaughtering poultry from 18 to 22 April, at a commercial poultry facility in Colorado where influenza A (H5N1) virus had been confirmed in the poultry.

Upon request of the organization providing personnel for culling of poultry at this facility, a respiratory sample was collected from the case on 20 April. The sample was received by the Colorado Department of Public Health and Environment Laboratory Services on 22 April and testing was completed on 25 April. Influenza A virus was detected by reverse transcriptase- polymerase chain reaction (RT-PCR). The sample was sent to the Influenza division of the United States Centers for Disease Control and Prevention (CDC) for further confirmation. Influenza A(H5) virus was confirmed by RT-PCR on 27 April and subtype N1 was subsequently confirmed by sequence analysis. 

On 26 April 2022, the patient was isolated and treated with antivirals. The patient did not report symptoms other than fatigue, was not hospitalized and has since recovered.

Public health response

On 20 April 2022, a total of nine samples from close contacts of the case and persons who participated in culling of poultry at the same facility were collected; all tested negative for influenza. Additional respiratory specimens were obtained on 28 April from the same nine contacts and tested negative for influenza. 

Virus characterization including genetic analysis to compare the virus sequence obtained from the human sample to virus sequences obtained from the poultry outbreak and antigenic analysis to compare with existing candidate H5 vaccine viruses are ongoing.

The close contacts of the patient have been recommended to receive influenza antiviral prophylaxis. The investigation is ongoing to determine if there are additional close contacts.

All individuals who were exposed to poultry and involved in depopulation activities at this facility are being monitored for symptoms for 10 days following the last date of their last exposure and will be tested if symptomatic in accordance with the US CDC guidelines and US Department of Agriculture guidance. Close contacts of the index case are also being monitored. 

Thus far, no evidence of human-to-human transmission of influenza A (H5N1) virus in this event has been identified.

WHO risk assessment

Since 2003 to 31 March 2022, a total of 864 cases and 456 deaths of influenza A(H5N1) human infection have been reported worldwide from 18 countries, however, this is the first reported case in the United States of America. The most recent case in humans prior to the current case, was reported in January 2022 in a case who had symptom onset in December 2021, from the United Kingdom of Great Britain and Northern Ireland. 

Whenever avian influenza viruses are circulating in poultry, there is a risk for sporadic infection and small clusters of human cases due to exposure to infected poultry or contaminated environments. Therefore, sporadic human cases are not unexpected.

The virus has not been detected in humans beyond this single case in the United States of America. Public health measures from both the human and animal health agencies have been implemented. Based on available information, WHO assesses the risk to the general population posed by this virus to be low and for occupationally exposed persons it is considered to be low-to-moderate. 

There are no specific vaccines for preventing influenza A(H5N1) in humans. Candidate vaccines to prevent influenza A(H5) virus infection in humans have been developed for pandemic preparedness purposes. Close analysis of the epidemiological situation, further characterization of the most recent viruses (human and poultry) and serological investigations are critical to assess associated risk and to adjust risk management measures in a timely manner.

WHO advice

This case does not change the current WHO recommendations on public health measures and surveillance of influenza.

Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global surveillance to detect and monitor virological, epidemiological and clinical changes associated with emerging or circulating influenza viruses that may affect human (or animal) health and timely virus sharing for risk assessment.

In the case of a confirmed or suspected human infection caused by a novel influenza virus with pandemic potential, including a variant virus, a comprehensive epidemiologic investigation (even while awaiting the confirmatory laboratory results) of history of exposure to animals, of travel, and contact tracing should be conducted. The epidemiologic investigation should include early identification of unusual respiratory events that could signal person-to-person transmission of the novel virus and clinical samples collected from the time and place that the case occurred should be tested and sent to a WHO Collaboration Center for further characterization.

When avian influenza viruses are circulating in an area, people involved in specific, high-risk tasks such as sampling sick birds, culling and disposing of infected birds, eggs, litters and cleaning of contaminated premises should be trained on the proper use of and provided with appropriate personal protective equipment (PPE). All persons involved in these tasks should be registered and monitored closely by local health authorities for seven days following the last day of contact with poultry or their environments.

Travelers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal feces. Travelers should also wash their hands often with soap and water. Travelers should follow good food safety and good food hygiene practices. Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community level spread is considered unlikely as this virus has not acquired the ability to transmit easily among humans.

All human infections caused by a novel influenza subtype are notifiable under the International Health Regulations (IHR) and State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic. Evidence of illness is not required for this report.

International travel or trade: WHO does not advise special traveler screening at points of entry or restrictions with regard to the current situation of influenza viruses at the human-animal interface.

 

Further information

Citable reference: World Health Organization (27 April 2022). Disease Outbreak News; Avian Influenza A (H5N1) – the United States of America. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2022-E000111

 

Ruotsin lintuinfluenssatilanne 2022

 https://www.sva.se/amnesomraden/smittlage/smittlage-for-fagelinfluensa/

 

Tämän vuoden villilintunäytteissä dominoi H5N1 lintuvirus . 

Etsivä löytää, sanotaan. Etsin loogisesti ala-alalinjaa BG ja löytyihän sitä! Se tarkoittaa BA.2.12.1 alalinjoja

 Kuvauksesta huomaa, ettää näitä kasvua osoitavia sub-sub-linjoja BG esiintyy BA.2 variantin alalinjassa BA.2.12.1.  Siinä vaiheesas alettiin ottaa käyttään  sub-sub-lineage merkinnät  (alalinjain alalinjain merkintä avuksi. BG ja siihen on jho kertynyt kolme linjaa BG.1, BG.2 ja BG.3.  Asioilla on edelleen avoimet  GITHUB-asiakoodit, numerot, joista  saa lisätietoa näistä asiainkäsittelyistä.    

BG. sai nimityksensä  nimityksensä 13 päivää sitten. 
Sitaatti GITHUB-sivulta: 

chrisruis commented 13 days ago

Thanks @LuisBarcenaF We now need new Pango lineages to be defined by at least one nonsynonymous mutation. We've therefore moved the start of this lineage one branch back in the tree so it includes several USA and UK sequences. We've therefore added this as BG.1 (with BG being an alias for BA.2.12.1) to start on the branch with A6458G (Orf1a:N2065D)

BG.2 sai määritelmänsä 9 päivää sitten.
Sitaatti GITHUB sivulta:

InfrPopGen commented 9 days ago

Thanks for submitting. We've added lineage BG.2 with 44 newly designated sequences, and 7 updated designations from BA.2.12.1. Defining mutation(s) G25352C (S:V1264L) and C29118T (N:T282I).

 

 BG.3 sai määritelmänsä 3 päivää sitten. .
 Sitaatti GITHUB sivulta:

InfrPopGen commented 3 days ago

Thanks for submitting. We've added lineage BG.3 with 28 newly designated sequences, and 1 updated designation from BA.2.12.1. Defining mutation(s) A9164G (Orf1a:T2967A).

Lineage Most common countries Earliest date # designated # assigned Description WHO Name
BG.1

37 0 Alias of B.1.1.529.2.12.1.1, Peru lineage, from pango-designation issue #679
BG.2

51 0 Alias of B.1.1.529.2.12.1.2, mainly found in USA, and Denmark, from pango-designation issue #767
BG.3

290Alias of B.1.1.529.2.12.1.3, mainly found in Peru, from pango-designation issue #784

BA.1 alalinjoissa oli myös tarvetta lyhennyksen merkintään BD.1, joka on BA.1.17.2 alalinjaa. .

 Tässä tutkittiin  kahta uutta kladia, josita toinen merkattiin alalinjaan BA.1.15 alalinjaksi BA.1.15.2. toinen taas  tarvitsei  jälleen lyhennysmerkinnän, koska sse kuului alalinjaan BA.1.17.2. Merkinnäksi tuli BD.1. Sitaatti asian käsittelystä.

chrisruis commented on 14 Apr

Thanks @corneliusroemer The US clade within BA.1.15 continued to exhibit growth compared to the rest of BA.1.15 so was designated BA.1.15.2 in #508

The UK clade within BA.1.17 has also grown steadily as a proportion of UK BA.1.17 sequences so does warrant a designation - will add this as BD.1 once we've checked for potential issues with second generation aliases


Näitä  määritelmiä on tullut  PANGO-listan puolelle näkyviin  kaksi viikkoa sitten. Yllä oleva  sitaatti on GITHUB- käsittelyn puolelta.  Alla  oleva sitaatti on PANGO-luettelon lpuolelta ( cov lineages)

 

BD.1

4404 designations
0 assignations
Alias of B.1.1.529.1.17.2.1, UK lineage, from pango-designation issue #461

BA.4 variantin alalinjat

 BA.4.1 näyttää saaneen  kaksi alalinjaa  kuluneen kuukauden aikana  PANGO-listoihin BA.4.1.1 ja BA.4.1.2 . Jälkimmäinen on merkattu  kaksi viikoa sitten.

https://github.com/cov-lineages/pango-designation/issues/614

 


LineageMost common countries Earliest date # designated # assigned Description WHO Name
BA.4 United States of America 30.0%, South_Africa 17.0%, United Kingdom 15.0%, Germany 7.0%, Israel 6.0% 2022-01-10 588 13334 Alias of B.1.1.529.4, from pango-designation issue #517 Omicron
BA.4.1

570 0 Alias of B.1.1.529.4.1, mainly found in South Africa, from pango-designation issue #548
BA.4.1.1

49 0 Alias of B.1.1.529.4.1.1, mainly found in South Africa and Germany, from pango-designation issue #667
BA.4.1.2

91 0 Alias of B.1.1.529.4.1.2, Austria lineage