2022年3月26日土曜日
Genomic surveillance of viral isolates during the 2013–2016 Ebola virus epidemic in Western Africa, the largest and most devastating filovirus outbreak on record, revealed several novel mutations. The responsible strain, named Makona, carries an A-to-V substitution at position 82 (A82V) in the glycoprotein (GP), which is associated with enhanced infectivity in vitro. Here, we investigated the mechanistic basis for this enhancement as well as the interplay between A82V and a T-to-I substitution at residue 544 of GP, which also modulates infectivity in cell culture. We found that both 82V and 544I destabilize GP, with the residue at position 544 impacting overall stability, while 82V specifically destabilizes proteolytically cleaved GP. Both residues also promote faster kinetics of lipid mixing of the viral and host membranes in live cells, individually and in tandem, which correlates with faster times to fusion following colocalization with the viral receptor Niemann-Pick C1 (NPC1). Furthermore, GPs bearing 82V are more sensitive to proteolysis by cathepsin L (CatL), a key host factor for viral entry. Intriguingly, CatL processed 82V variant GPs to a novel product with a molecular weight of approximately 12,000 (12K), which we hypothesize corresponds to a form of GP that is pre-triggered for fusion. We thus propose a model in which 82V promotes more efficient GP processing by CatL, leading to faster viral fusion kinetics and higher levels of infectivity.
The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets
During 2013-2016, a novel isolate of Ebola virus (EBOV-Makona) caused an epidemic in West Africa. The virus was distinct from known EBOV strains (EBOV-Kikwit and EBOV-Mayinga), which were responsible for previous outbreaks in Central Africa. To investigate the pathogenicity of EBOV-Makona, we engineered and rescued an early isolate (H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07, called rgEBOV-C07) using an updated reverse-genetics system. rgEBOV-C07 was found to be highly pathogenic in both the knockout mouse and ferret models, with median lethal dose values of 0.078 and 0.015 plaque-forming units, respectively. Therefore, these animals are appropriate for screening potential countermeasures against EBOV-Makona without the need for species adaptation.https://pubmed.ncbi.nlm.nih.gov/29878131/
Is Ebola Evolving Into a Deadlier Virus?
virus apparently moved out of some wild creature, Ebola’s natural host—in this case, probably a bat—and entered the bloodstream of an as yet unidentified person. From that person, the virus began spreading through the local population. Ebola can overwhelm the human immune system in a matter of days. Symptoms typically include vomiting, diarrhea, coughing, rash, dementia, hemorrhages, and hiccups. Death occurs like the slamming of a door, when the patient abruptly goes into shock.
The Kivu Ebola outbreak area is in a conflict zone, beset by armed militias and ethnic violence. Local people often don’t trust the international medical organizations that run the Ebola treatment centers. There have been at least a hundred and ninety-four attacks on local health workers, seven of whom have been killed. Watson-Stryker, the researcher, said that social media complicates containment and treatment efforts. Conspiracy theories about medical workers and false information about how the virus is spread are ricocheting around popular platforms like WhatsApp. “The problem is the post-factual reality that exists in social media,” she said.
An effective experimental vaccine for Ebola exists, and more than a hundred and seventy-five thousand people have received it. Even so, the virus is finding new victims and extending its geographic range. Three cases of Ebola recently appeared in Uganda, and there have now been four cases in the Congolese city of Goma, which has roughly two million residents and is situated on the border with Rwanda. The W.H.O. recently estimated that more than two hundred million dollars in emergency funding would be needed to bring the virus under control. That money hasn’t been raised yet.
An Ebola particle is a very small, filament-shaped object, made of six different structural proteins. Ebola’s genetic code, or genome, is contained in a strand of ribonucleic acid, or RNA, that is coiled tightly in the core of the particle. The genome, which has some nineteen thousand letters in it, holds the master designs of Ebola’s proteins.
RNA viruses—which range from Ebola to measles and influenza— tend to produce errors, or mutations, in their code when they copy themselves. Most mutations are either bad for the virus or have no effect on it. Every now and then, however, a virus gets a mutation that benefits it. In fact, the production of errors during copying plays an important role in the long-term survival of viruses. As time goes by and the virus makes inaccurate copies of itself, slightly different varieties of the virus arise. The different varieties are called lineages. They can be imagined as moths of the same species whose wings are slightly different colors. Some wing colors help a moth camouflage itself more effectively, be eaten less often by predators, and survive longer than moths of other colors. Those types of moths go on to reproduce successfully, while moths of other colors eventually die out, until the population of moths has changed color entirely. This is the process of evolution.
Considered as a life-form, the Kivu Ebola isn’t a single organism but, rather, an immense swarm of particles that jumps from victim to victim. Each particle in the swarm possesses a biological drive to copy itself. As the particles copy themselves, they compete with all the other particles for survival. Ebola particles copy themselves every eighteen hours. This is the generation time of the virus—the time it takes for a particle of Ebola to get inside a human cell and potentially create thousands of identical copies of itself in the cell. The copies then exit the infected cell and drift into the bloodstream, infecting more cells. Early in the disease, Ebola patients tend to get sicker in downward lurches. In some patients, the lurches are spaced roughly eighteen hours apart, as each new generation of particles floods the body. An infected person’s bodily fluids are lethally infectious, because they are filled with Ebola particles. If some of those particles get into new people, the virus spreads.
By now, the Kivu Ebola swarm has been going through its eighteen-hour replication cycle in humans for more than a year. Some virologists wonder whether Kivu Ebola could start evolving, or whether it has already started to evolve, in a way that makes it more dangerous to people—perhaps by becoming more contagious, in which case it would get much harder to control. These questions introduce a new aspect to the international emergency.
During the Ebola epidemic that ravaged West Africa in 2014 and 2015, that form of Ebola showed possible signs of evolving. Virologists are still trying to determine the significance of what happened. The epidemic began in a village in Guinea, in December, 2013, when some particles of Ebola apparently went from a bat into a small boy. That strain of the virus, now referred to as Makona Ebola, killed the boy and most of his family, and then began spreading. In the end, around thirty thousand people were infected and more than eleven thousand died before Makona Ebola was finally brought under control and eliminated from the human population. (There were eleven cases in the United States.)
As the epidemic progressed, a team of researchers, led by Pardis Sabeti, a genomic scientist at Harvard and the Broad Institute, studied the genetic code of various samples of Ebola taken from the blood of people who had been infected. They found that the virus began mutating as soon as it got into people. “From the outset, I was intrigued by the large number of mutations we found,” Sabeti told me. Makona Ebola quickly developed into several basic varieties. Then, in late May, 2014, one of the lineages took off like a wildfire and spread rapidly all over Sierra Leone and Liberia. This lineage is named the A82V Makona Variant of Ebola. For simplicity, I’ll call it the Makona mutant. The majority of patients in the epidemic were infected with the Makona mutant, including all eleven individuals in the United States. Meanwhile, the other lineages of Ebola died out. It seemed that the Makona mutant had somehow beaten them in a contest for survival.
Sabeti and other research groups noted that the change in the code of the Makona mutant happened in a single letter, which was part of the genetic recipe that causes the Ebola particle to be covered in roughly three hundred soft, squishy knobs. The knobs, called glycoproteins, are essential for the particle’s survival; they help it stick to cells and get inside cells, where it can reproduce. Sabeti wondered if the change in the knob protein could help this particular lineage of Ebola survive and prosper. “The mutation showed up at an inflection point in the outbreak, just as the outbreak exploded,” Sabeti said. “This was really intriguing.” It seemed that there might be something different about the knobs on the outside of the Makona mutant.
In 2016, a research team at the University of Massachusetts Medical School, led by a doctor named Jeremy Luban, ran some experiments on the Makona-knob protein. The team found that the knobs on the Makona mutant were four to five times better at invading human cells than those on the earlier strain of Makona. The Makona mutant stuck to human cells like a magnet, and the knobs seemed able to open a cell’s outer membrane, with the ease of a slide opening the teeth of a zipper, to allow the virus inside. “But what the significance of this mutation is for the outbreak, and how deadly this virus is, are still open questions,” Luban told me. “In biology, there is almost no such thing as proof.” Luban is planning more experiments to try to find out whether the Makona mutant was, in fact, more devastating or contagious than its predecessor.
A British team led by a virologist at the University of Nottingham named Jonathan Ball found that the Makona mutant seemed to be around twice as infectious in human cells than the earlier version of the virus had been. It also was less infectious in bat cells. The Makona mutant seemed to be evolving away from bats and turning into a virus suited for human cells. “I wasn’t at all surprised by this,” Ball said. “If you put a virus in a different system, you quickly see that the virus adapts to the new environment. I was surprised that other people were surprised.” Ball stressed that the experiments had been done in test tubes, using knobs of Ebola grafted onto a harmless virus. “We can’t show how the [real] virus will actually behave in a human,” he said. “You can’t do that experiment.” Many scientists, including Ball and Luban, aren’t so sure that the Makona mutant was any more dangerous than any other form of Ebola. The Makona mutant most likely spread far and wide because of social and behavioral factors, but it may have spread faster and more widely than it would have otherwise because of a change in one part of its genome.
What about the Kivu Ebola? The violence in the outbreak area makes doing scientific research there difficult. Nevertheless, a Congolese team of genomic researchers at the National Institute for Biomedical Research, at the University of Kinshasa, working with international colleagues, has been collecting blood samples from the outbreak and reading the genetic code of the Ebola. The Kivu Ebola, so far, has mutated into four lineages. Three of the four are active in the population. The swarm is exploring people’s immune systems and jumping from one victim to the next. So far, none of the three active varieties has become dominant. “The virus has been brewing in that area for a while,” Sabeti said. “If you give Ebola enough time to transmit from human to human, then an unpredictable event can occur. How likely is it that Ebola could change suddenly? We don’t have a good answer to that question.”
Right now, there may be around six hundred people in eastern Congo who have Kivu Ebola particles replicating in their bodies. As Ebola re-creates itself, many of the resulting particles are deformed duds and can’t replicate further. The ones that can copy themselves are infective. The Kivu swarm, with its three new lineages of Ebola, may amount to about one or two quadrillion infective particles of the virus. If these particles were collected in one place, they would fill three teaspoons and would weigh about fifteen grams. That small space contains numberless genetic possibilities. The longer the outbreak is allowed to continue, the greater the chances that Ebola will mutate, get better at spreading in humans, and vastly enlarge its circle of victims.
https://www.newyorker.com/science/elements/is-ebola-evolving-into-a-more-deadly-virus
Canada’s top microbiology lab sent fifteen “deadliest pathogens” to the Wuhan lab months before the Coronavirus outbreak: Report
The Canadian Lab has, however, said that the shipments had nothing to do with the coronavirus outbreak and moreover it said that the termination of the Chinese scientist, Dr Xiangguo Qiu from the Winnipeg lab was also not related to the shipment.
17 June, 2020
Newly-released access-to-information documents have revealed shocking details of how a shipment of deadly pathogens from Canada’s National Microbiology Lab in Winnipeg was received by the Wuhan Institute of Virology, months before the outbreak of coronavirus pandemic. It is being reported that the delivery of 15 different lethal pathogens was made in May 2019.
According to a report by CBC News, the scientist who was responsible for exporting the pathogens to China was sacked after an investigation in July last year. Dr Xiangguo Qiu, the person who was allegedly behind this delivery, was terminated from Canada’s only level-4 lab over what the lab called a possible “policy breach”. Earlier it was reported that Canada had dispatched Ebola and Henipah viruses to the Wuhan lab.
The documents show that a total of 15 different virus samples were sent from Canada to the Chinese laboratory, each in two vials. The pathogens were:- Ebola Makona (three different varieties), Mayinga, Kikwit, Ivory Coast, Bundibugyo, Sudan Boniface, Sudan Gulu, MA-Ebov, GP-Ebov, GP-Sudan, Hendra, Nipah Malaysia and Nipah Bangladesh.
The documents accessed by CBC show that Canadian scientists were about the send the virus samples in an incorrect packaging on a commercial Air Canada flight on March 31, 2019. But correct packaging was used only after the Chinese side pointed out that Canadians are using the wrong packaging to ship the deadly pathogens.
Canada denies connection between the virus shipment and coronavirus outbreak
The Canadian Lab has, however, said that the shipments had nothing to do with the coronavirus outbreak and moreover it said that the termination of the Chinese scientist, Dr Xiangguo Qiu from the Winnipeg lab was also not related to the shipment.
The chief of media relations for Health Canada and the Public Health Agency of Canada, Eric Morrissette, wrote in an email: “The administrative investigation is not related to the shipment of virus samples to China.
“In response to a request from the Wuhan Institute of Virology for viral samples of Ebola and Henipah viruses, the Public Health Agency of Canada (PHAC) sent samples for the purpose of scientific research in 2019.”
Along with PHAC, the Royal Canadian Mounted Police (RCMP) has also denied any connections between the pandemic and the virus shipments. There is no evidence linking this shipment to the spread of the coronavirus. Ebola is a filovirus and Henipa is a paramyxovirus; no coronavirus samples were sent.
Despite the Canadian media reports, the Chinese side has also never officially disclosed any information about the alleged virus transfer from Canada.
Despite clarifications, experts are not convinced. Amir Attaran, a law professor and epidemiologist at the University of Ottawa, was quoted by CBC News as saying: “It is suspicious. It is alarming. It is potentially life-threatening.”
Experts displeased by the Canadian Government’s decision to export the pathogens to China
Alarmed by the act, Amir Attaran said that the shipment was sent to the Chinese lab knowing that it has links to the Chinese military: “What we know is that before she was removed, she sent one of the deadliest viruses on Earth, and multiple varieties of it to maximise the genetic diversity and maximise what experimenters in China could do with it, to a laboratory in China that does dangerous gain of function experiments. And that has links to the Chinese military,” Attaran said.
Talking about the “gain of function experiment”, in which a natural pathogen is taken into the lab, made to mutate, and then assessed to see if it has become more deadly or infectious, the law professor furthered: “The Wuhan lab does them and we have now supplied them with Ebola and Nipah viruses. It does not take a genius to understand that this is an unwise decision. I am extremely unhappy to see that the Canadian government shared that genetic material,” said Attaran.
Though the Canadian officials have consistently denied any connections between the COVID-19 pandemic and the virus shipments and stated that there is no evidence linking the shipments to the spread of the coronavirus, given the fact that the pandemic is said to have originated in Wuhan, news of the “policy breach” is a cause of concern. Especially considering that the revelation has come during the time when the diplomatic relationship between China and the West remains volatile.
While America has repeatedly blamed China for its campaign of “disinformation” related to the coronavirus, Tobias Ellwood, an MP of the United Kingdom, in an exclusive interview with Express.co.uk, said: “COVID-19, if it’s done anything, it has woken up the world to this rather aggressive and concerning the objective of China wanting to quietly advance its own influence across the world.”
https://www.opindia.com/2020/06/canadas-top-microbiology-lab-sent-fifteen-deadliest-pathogens-to-the-wuhan-lab-months-before-the-coronavirus-outbreak-report/
Canadian scientist sent deadly viruses to Wuhan lab months before RCMP asked to investigate
Documents show concerns about Ebola shipment from National Microbiology Lab, no relation to COVID-19
CBC News ·
Newly-released access-to-information documents reveal details
about a shipment of deadly pathogens last year from Canada's National
Microbiology Lab to China — confirming for the first time who sent them,
what exactly was shipped, and where it went.
CBC News had already reported about the shipment of
Ebola and Henipah viruses but there's now confirmation one of the
scientists escorted from the lab in Winnipeg amid an RCMP investigation
last July was responsible for exporting the pathogens to the Wuhan
Institute of Virology four months earlier.
Dr.
Xiangguo Qiu, her husband Keding Cheng and her students from China were
removed from Canada's only level-4 lab over what's described as a
possible "policy breach." The Public Health Agency of Canada had asked
the RCMP to get involved several months earlier.
The virus shipments are not related to the outbreak of COVID-19 or research into the pandemic, Canadian officials said.
PHAC said the shipment and Qiu's eviction from the lab are not connected.
https://www.cbc.ca/news/canada/manitoba/canadian-scientist-sent-deadly-viruses-to-wuhan-lab-months-before-rcmp-asked-to-investigate-1.5609582
Documents show concerns about Ebola shipment from National Microbiology Lab, no relation to COVID-19
CBC News ·
Newly-released access-to-information documents reveal details about a shipment of deadly pathogens last year from Canada's National Microbiology Lab to China — confirming for the first time who sent them, what exactly was shipped, and where it went.
CBC News had already reported about the shipment of Ebola and Henipah viruses but there's now confirmation one of the scientists escorted from the lab in Winnipeg amid an RCMP investigation last July was responsible for exporting the pathogens to the Wuhan Institute of Virology four months earlier.
Dr. Xiangguo Qiu, her husband Keding Cheng and her students from China were removed from Canada's only level-4 lab over what's described as a possible "policy breach." The Public Health Agency of Canada had asked the RCMP to get involved several months earlier.
The virus shipments are not related to the outbreak of COVID-19 or research into the pandemic, Canadian officials said.
PHAC said the shipment and Qiu's eviction from the lab are not connected.
https://www.cbc.ca/news/canada/manitoba/canadian-scientist-sent-deadly-viruses-to-wuhan-lab-months-before-rcmp-asked-to-investigate-1.5609582
2022年3月23日水曜日
武漢で本当は何が起きたのか?
3 件のコメント:
アフリカに拠点も置く
野生動物見る体の旅行もやってる
NGOみたいな組織団体のつべを見ると
最近の動画には自動車が鈴なりで
ノーマスクな方々がリアルハンティング見物
マスクもパスも全制限撤廃な欧州から続々と
多分行く事ないから
リアルアフリカ野生動物動画
視聴出来て有難いけれども
近い将来そんな旅行も業者も
消失して彼らも★になるのかー
病原菌いじって
ひゃっほーとかいってる
おバカ研究者たちの
顔が目に浮かびます
合掌
>まあワクチン推進派も反対派ももうマスクなんてイラネとか言ってますがね
接種者はどんどん真に受けてほちーーーーーーーぃwwwww
て早く★になれなれサンからすれば言いたいが
エボラは死んでからの扱いが間違えたら貰い事故死するからなー
>系統の1つが山火事のように離陸
>コウモリ細胞では感染性も低
wwwwwwwwwwwwww人為でなければ説明つかないよね
>カナダがエボラウイルスとヘニパウイルスを武漢研究所に派遣した
世界の工場が世界の研究所でしたと同時通訳してあげてほちー
良いコかどうかは自信ありまちぇんが、マスクはしますよこれからも
ムカつく奴には笑顔がステキ~マスク外れる時は強みだね~とか言って
蛇見習って囁くようにするかもしれん
コメントを投稿