This coronavirus mutation has taken over the world. Scientists are trying to understand why.
Health-care workers from University of South Florida Health administer coronavirus testing June 25 at a community center in Tampa. (Octavio Jones/Getty Images)
When the first coronavirus cases in Chicago appeared in January, they bore the same genetic signatures as a germ that emerged in China weeks before.
But as Egon Ozer, an infectious-disease specialist at the Northwestern University Feinberg School of Medicine, examined the genetic structure of virus samples from local patients, he noticed something different.
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A change in the virus was appearing again and again. This mutation, associated with outbreaks in Europe and New York, eventually took over the city. By May, it was found in 95 percent of all the genomes Ozer sequenced.
At a glance, the mutation seemed trivial. About 1,300 amino acids serve as building blocks for a protein on the surface of the virus. In the mutant virus, the genetic instructions for just one of those amino acids — number 614 — switched in the new variant from a “D” (shorthand for aspartic acid) to a “G” (short for glycine).
But the location was significant, because the switch occurred in the part of the genome that codes for the all-important “spike protein” — the protruding structure that gives the coronavirus its crownlike profile and allows it to enter human cells the way a burglar picks a lock.
And its ubiquity is undeniable. Of the approximately 50,000 genomes of the new virus that researchers worldwide have uploaded to a shared database, about 70 percent carry the mutation, officially designated D614G but known more familiarly to scientists as “G.”
“G” hasn’t just dominated the outbreak in Chicago — it has taken over the world. Now scientists are racing to figure out what it means.
At least five laboratory experiments suggest that the mutation makes the virus more infectious, although only one of those studies has been peer-reviewed. That study, led by scientists at Los Alamos National Laboratory and published Thursday in the journal Cell, also asserts that patients with the G variant actually have more virus in their bodies, making them more likely to spread it to others.
The mutation doesn’t appear to make people sicker, but a growing number of scientists worry that it has made the virus more contagious.
“The epidemiological study and our data together really explain why the [G variant’s] spread in Europe and the U.S. was really fast,” said Hyeryun Choe, a virologist at Scripps Research and lead author of an unpublished study on the G variant’s enhanced infectiousness in laboratory cell cultures. “This is not just accidental.”
But there may be other explanations for the G variant’s dominance: biases in where genetic data are being collected, quirks of timing that gave the mutated virus an early foothold in susceptible populations.
“The bottom line is, we haven’t seen anything definitive yet,” said Jeremy Luban, a virologist at the University of Massachusetts Medical School.
The scramble to unravel this mutation mystery embodies the challenges of science during the coronavirus pandemic. With millions of people infected and thousands dying every day around the world, researchers must strike a high-stakes balance between getting information out quickly and making sure that it’s right.
A better lock pick
SARS-CoV-2, the novel coronavirus that causes the disease covid-19, can be thought of as an extremely destructive burglar. Unable to live or reproduce on its own, it breaks into human cells and co-opts their biological machinery to make thousands of copies of itself. That leaves a trail of damaged tissue and triggers an immune system response that for some people can be disastrous.
This replication process is messy. Even though it has a “proofreading” mechanism for copying its genome, the coronavirus frequently makes mistakes, or mutations. The vast majority of mutations have no effect on the behavior of the virus.
But since the virus’s genome was first sequenced in January, scientists have been on the lookout for changes that are meaningful. And few genetic mutations could be more significant than ones that affect the spike protein — the virus’s most powerful tool.
This protein attaches to a receptor on respiratory cells called ACE2, which opens the cell and lets the virus slip inside. The more effective the spike protein, the more easily the virus can break into the bodies of its hosts. Even when the original variant of the virus emerged in Wuhan, China, it was obvious that the spike protein on SARS-CoV-2 was already quite effective.
But it could have been even better, said Choe, who has studied spike proteins and the way they bind to the ACE2 receptor since the severe acute respiratory syndrome outbreak in 2003.
The spike protein for SARS-CoV-2 has two parts that don’t always hold together well. In the version of the virus that arose in China, Choe said, the outer part — which the virus needs to attach to a human receptor — frequently broke off. Equipped with this faulty lock pick, the virus had a harder time invading host cells.
“I think this mutation happened to compensate,” Choe said.
Studying both versions of the gene using a proxy virus in a petri dish of human cells, Choe and her colleagues found that viruses with the G variant had more spike proteins, and the outer parts of those proteins were less likely to break off. This made the virus approximately 10 times more infectious in the lab experiment.
The mutation does not seem to lead to worse outcomes in patients. Nor did it alter the virus’s response to antibodies from patients who had the D variant, Choe said, suggesting that vaccines being developed based on the original version of the virus will be effective against the new strain.
Choe has uploaded a manuscript describing this study to the website bioRxiv, where scientists can post “preprint” research that has not yet been peer reviewed. She has also submitted the paper to an academic journal, which has not yet published it.
The distinctive infectiousness of the G strain is so strong that scientists have been drawn to the mutation even when they weren’t looking for it.
Neville Sanjana, a geneticist at the New York Genome Center and New York University, was trying to figure out which genes enable SARS-CoV-2 to infiltrate human cells. But in experiments based on a gene sequence taken from an early case of the virus in Wuhan, he struggled to get that form of the virus to infect cells. Then the team switched to a model virus based on the G variant.
“We were shocked,” Sanjana said. “Voilà! It was just this huge increase in viral transduction.” They repeated the experiment in many types of cells, and every time the variant was many times more infectious.
Their findings, published as a preprint on bioRxiv, generally matched what Choe and other laboratory scientists were seeing.
But the New York team offers a different explanation as to why the variant is so infectious. Whereas Choe’s study proposes that the mutation made the spike protein more stable, Sanjana said experiments in the past two weeks, not yet made public, suggest that the improvement is actually in the infection process. He hypothesized that the G variant is more efficient at beginning the process of invading the human cell and taking over its reproductive machinery.
Luban, who has also been experimenting with the D614G mutation, has been drawn to a third possibility: His experiments suggest that the mutation allows the spike protein to change shape as it attaches to the ACE2 receptor, improving its ability to fuse to the host cell.
Different approaches to making their model virus might explain these discrepancies, Luban said. “But it’s quite clear that something is going on.”
Unanswered questions
Although these experiments are compelling, they’re not conclusive, said Kristian Andersen, a Scripps virologist not involved in any of the studies. The scientists need to figure out why they’ve identified different mechanisms for the same effect. All the studies still have to pass peer review, and they have to be reproduced using the real version of the virus.
Even then, Andersen said, it will be too soon to say that the G variant transmits faster among people.
Cell culture experiments have been wrong before, noted Anderson Brito, a computational biologist at Yale University. Early experiments with hydroxychloroquine, a malaria drug, hinted that it was effective at fighting the coronavirus in a petri dish. The drug was touted by President Trump, and the Food and Drug Administration authorized it for emergency use in hospitalized covid-19 patients. But that authorization was withdrawn this month after evidence showed that the drug was “unlikely to be effective” against the virus and posed potential safety risks.
So far, the biggest study of transmission has come from Bette Korber, a computational biologist at Los Alamos National Laboratory who helped build one of the world’s biggest viral genome databases for tracking HIV. In their paper published this week, Korber’s team argues that the G variant “may have a fitness advantage” that explains its overwhelming dominance.
Using two statistical approaches, the researchers analyzed some 30,000 sequences from across the world; they found that most places where the original virus was dominant before March were eventually taken over by the mutated version. This switch often took place in a matter of weeks. This was especially apparent in the United States: Ninety-six percent of early sequences here belonged to the D variant, but by the end of March, more than two thirds of sequences carried the G amino acid instead.
Korber’s collaborators in the U.K. also found evidence that people with the G variant had more viral particles in their bodies. Although this higher viral load didn’t seem to make people sicker, it might explain the G variant’s rapid spread, the scientists wrote. People with more virus to shed are more likely to infect others.
Meanwhile, the paper describes two laboratory experiments confirming what Sanjana, Choe and others have found: the G variant was 3 to 6 times more infectious.
A preliminary version of the Los Alamos paper, which did not include these laboratory findings, drew intense scrutiny when it was released as a pre-print in the spring. Though the additional data and the credibility of peer review make the case for increased transmissibility even stronger, many scientists — including Korber — say more research is needed.
“There are so many biases in the data set here that you can’t control for and you might not know exist,” Andersen said. In a time when as many as 90 percent of U.S. infections are still undetected and countries with limited public health infrastructure are struggling to keep up with surging cases, a shortage of data means “we can’t answer all the questions we want to answer.”
Pardis Sabeti, a computational biologist at Harvard University and the Broad Institute, noted that the vast majority of sequenced genomes come from Europe, where the G variant first emerged, and the United States, where infections thought to have been introduced by travelers from Europe spread undetected for weeks before the country shut down. This could at least partly explain why it appears so dominant.
The mutation’s success might also be a “founder effect,” she said. Arriving in a place like Northern Italy — where the vast majority of sequenced infections are caused by the G variant — it found easy purchase in an older and largely unprepared population, which then unwittingly spread it far and wide.
Scientists may be able to rule out these alternative explanations with more rigorous statistical analyses or a controlled experiment in an animal population. And as studies on the D614G mutation accumulate, researchers are starting to be convinced of its significance.
“I think that slowly we’re beginning to come to a consensus,” said Judd Hultquist, a virologist at Northwestern University.
Solving the mystery of the D614G mutation won’t make much of a difference in the short term, Andersen said. “We were unable to deal with D,” he said. “If G transmits even better, we’re going to be unable to deal with that one.”
But it’s still essential to understand how the genome influences the behavior of the virus, scientists say. Identifying emerging mutations allows researchers to track their spread. Knowing what genes affect how the virus transmits enables public health officials to tailor their efforts to contain it. Once therapeutics and vaccines are distributed on a large scale, having a baseline understanding of the genome will help pinpoint when drug resistance starts to evolve.
“Understanding how transmissions are happening won’t be a magic bullet, but it will help us respond better,” Sabeti said. “This is a race against time.”
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پریست لایت روم موبایل
ما تو سایت abasvp.ir بیش از چند صد مجموعه
پریست لایتروم,فتوشاپ موبایل با فرمت DNG برای شما قرار دادیم و نیز روزانه بهترین پریست ها رو گلچین کرده و برای
دانلود رو سایت قرار میدیم.که بتونید براحتی دانلود کرده و رو لایت
روم موبایل نصب و رو عکس هاتون ادیت
زیبای اعمال کنید.
پریست موبایل
لایت روم موبایل
لایتروم موبایل یکی از بهترین اپلیکشن ادیت عکس تو موبایل ها هستش که بسیاری از
امکانات لایتروم و کمرا راو فتوشاپ رو تو یه اپ
رایگان به شما میده که بتونید براحتی عکس هاتون رو ادیت کنید و از اونجای که ادیت رنگی عکس دانش و تجریه
خاصی میخواد. شما میتونید از از تنظیمات بیش آماده
(پریست) تو لایت روم موبایل استفاده کنید
پریست لایت روم موبایل
امروزه پریست ها ،کار را برای عکاسان ،وبلاگ
نویسان ،اینفلوئنسرها و به طور کلی کسانی که
به دنبال زیبا کردن عکس هایشان هستند راحت کرده
به خصوص اینکه می شود به راحتی آنها را در داخل
گوشی و با یک کلیک به راحتی در عرض
چند ثانیه و در هر مکان ادیت و
ویرایش کرد.
پریست لایت روم موبایل رایگان
شما می تونید با پرداخت هزینه ناچیز از پریست های
سایت Abasvp.ir استفاده کنید . ما بهترین و حرفه ای ترین پریست های لایت
روم موبایل رو گردآوری کرده
ایم .
نصب پریست لایت روم موبایل
برنامه Lightroom CC Mobile را بارگیری
کرده و اگر قبلاً آن را انجام نداده اید ، یک حساب کاربری رایگان ایجاد کنید.
فایل زیپ پریست خود را از حالت فشرده خارج کنید.
پوشه پریست تلفن همراه را باز کنید.
( برنامه ای که برای باز کردن فایل ها ما می توانیم به شما پیشنهاد بدیم ، izip است.)
فایل های DNG خود را انتخاب کنید و
به لایت روم انتقال دهید.
برنامه لایت روم را باز کنید و فایل هایی که انتقال داده اید رو می توانید به صورت عکس مشاهده کنید.
عکس را باز کرده ،بر روی تنظیمات… (گوشه بالا سمت راست) کلیک کنید.از گزینههایی که
نمایش داده می شود، روی Create Preset کلیک کنید.
این مرحله شما از قسمت Preset
Name نام پریست و از قسمت Preset Group
گروهی که دوست دارین پریست در آن ذخیره شود را انتخاب کنید.
تبریک میگیم ، شما توانستید پریست ها را در برنامه ذخیره
کنید اما هنوز بخش هیجان انگیزش در راه هست…
پریست برای لایت روم موبایل
لایت روم موبایل
شما می توانید در سایت ما پریست برای
لایت روم موبایل را به راحتی
دانلود کنید و مطمئن باشید که بهترین
پریست را جمع کرده ایم و با پرداخت هزینه ای ناچیز از تمامی امکانات بهره مند شوید .
آموزش نصب پریست لایت روم موبایل
برنامه Lightroom CC Mobile را بارگیری کرده و اگر قبلاً آن را انجام
نداده اید ، یک حساب کاربری رایگان ایجاد کنید.
فایل زیپ پریست خود را از حالت فشرده خارج کنید.
پوشه پریست تلفن همراه را باز کنید.
( برنامه ای که برای باز کردن فایل ها ما می توانیم به شما پیشنهاد بدیم ، izip است.)
فایل های DNG خود را انتخاب کنید و به لایت روم انتقال دهید.
برنامه لایت روم را باز کنید و فایل هایی که انتقال داده اید رو می توانید به صورت عکس مشاهده
کنید.
عکس را باز کرده ،بر روی تنظیمات… (گوشه بالا سمت راست) کلیک کنید.از گزینههایی که نمایش داده می شود،
روی Create Preset کلیک کنید.
این مرحله شما از قسمت Preset Name نام پریست
و از قسمت Preset Group گروهی که دوست دارین پریست در آن ذخیره شود را انتخاب کنید.
تبریک میگیم ، شما توانستید پریست ها را در برنامه ذخیره کنید اما
هنوز بخش هیجان انگیزش در راه هست…
ذخیره پریست در لایت روم موبایل
در بالا نحوه ذخیره پریست در لایت روم موبایل آموزش داده شد .
دانلود پریست لایت روم نسخه موبایل
شما در سایت abasvp.ir می توانید بهترین پریست های نسخه موبایل رو
دانلود کنید و استفاده کنید که در بالا نحوه استفاده رو به شما آموزش داده ایم .
دانلود پریست برای لایت روم موبایل
در سایت abasvp می توانید دانلود پریست برای لایت
روم موبایل رو دانلود کنید و براحتی طبق آموزش استفاده کنید .
دانلود پریست های لایت روم موبایل
دانلود پریست های لایت روم موبایل چیزی که به دنبال آن هستید در این
سایت یافت می شود .شما می توانید با پرداخت هزینه ای ناچیز این
پریست ها را دانلود کنید . و براحتی تمام
استفاده کنید اگر پریستی مد نظر شما باشد و در سایت موجود
نباشد می توانید از طریق واتزاپ درخواست
خودتون رو ثبت کنید .
خرید پریست لایت روم موبایل
خرید پریست لایت روم موبایل براحتی تمام در سایت abasvp قابل انجام هست و می توانید با هزینه
ای کم تمامی پریست های سایت را دانلود
کنید .
آموزش استفاده از پریست در لایت روم موبایل
برنامه Lightroom CC Mobile را بارگیری کرده
و اگر قبلاً آن را انجام
نداده اید ، یک حساب کاربری رایگان
ایجاد کنید.
فایل زیپ پریست خود را از حالت فشرده خارج کنید.
پوشه پریست تلفن همراه را باز کنید.
( برنامه ای که برای باز کردن فایل
ها ما می توانیم به شما پیشنهاد بدیم ، izip
است.)
فایل های DNG خود را انتخاب کنید و به لایت روم
انتقال دهید.
برنامه لایت روم را باز کنید و فایل
هایی که انتقال داده اید رو می توانید به صورت عکس مشاهده کنید.
عکس را باز کرده ،بر روی تنظیمات… (گوشه بالا سمت راست) کلیک
کنید.از گزینههایی که نمایش داده می شود،
روی Create Preset کلیک کنید.
این مرحله شما از قسمت Preset Name نام پریست
و از قسمت Preset Group گروهی که دوست دارین پریست در آن ذخیره شود را انتخاب کنید.
تبریک میگیم ، شما توانستید پریست ها را
در برنامه ذخیره کنید اما هنوز بخش هیجان انگیزش در راه هست…
افزودن پریست به لایت روم
موبایل
افزودن پریست به لایت روم موبایل در بالا توضیح داده
شد .
اضافه كردن پريست به لايت روم موبایل
اضافه کردن پریست به لایت روم موبایل در
بالا توضیح داده شد .
دانلود پریست لایت روم برای موبایل
شما می توانید در سایت Abasvp.ir دانلود پریست لایت روم برای موبایل را به راحتی انجام دهید و
فقط یک اشتراک ثبت کنید و به تمامی فایل
ها دسترسی خواهید داشت .
دانلود پریست رایگان برای لایت روم
موبایل
دانلود پریست با خرید اشتراک با قیمتی بسیار کم امکان پذیر است
. برای این پریست ها و گلچین کردن آن ها زحمت بسیاری
کشیده شده است .
دانلود پریست پرتره لایت روم موبایل
دانلود پریست های لایت روم حرفه ای عکس
پرتره Dope Portrait Lightroom Presets مجموعه ای از پریست حرفه ای عکاسی برای لایت روم دسکتاپ و موبایل
در سایت abasvp امکان پذیر است.
دانلود پریست پاییزی لایت روم موبایل
پریست ها، افکت های از پیش ساخته شده ای هستند که با اجرای آن ها تنظیمات
خاصی روی عکس های شما اعمال می شود.
شما می توانید به کمک پریست ها
و با نصب ساده ی آنها، تصاویر خود را به راحتی تغییر دهید و جلوه های زیبایی
را بر روی آن ها اعمال نمائید.
این پکیج تمام مواردی که برای بهبود
تصاویر مربوط به پاییز لازم است را دارا می باشد و می تواند نمای خاصی را به آنها اعطا کند.
همچنین شما می توانید تصاویر مربوط به سایر فصل ها را به کمک این پریست ها به نمای پاییزی تبدیل کنید و از تغییر
حالت آنها لذت ببرید.
این پریست ها مخصوص نرم افزار Lightroom
می باشند و استفاده ی آسانی نیز دارد
قابل استفاده برای تمامی طراحان آلبوم دیجیتال و
طراحان بروشورهای تبلیغاتی و آتلیه های عکاسی
با شخصی سازی پریست ها ی مجموعه میتوانید آنها را با سلیقه خود ذخیره نمایید
پریست اماده لایت روم موبایل
پریست اماده لایت روم موبایل در سایت abasvp امکان پذیر هست و می توان با خرید اشتراک به پریست ها
دسترسی داشت .
دانلود پریست لایت روم موبایل
دانلود پریست لایت روم موبایل اینجا می توان با تهیه اشتراک
ویژه دانلود و استفاده کرد .
دانلود پریست لایت روم موبایل رایگان
دانلود پریست لایتروم موبایل با خرید اشتراک با قیمتی بسیار کم امکان پذیر است .
برای این پریست ها و گلچین کردن آن ها زحمت بسیاری کشیده شده است .
پریست های رایگان لایت روم موبایل
پریست های رایگان لایت روم با خرید اشتراک با قیمتی بسیار کم امکان پذیر است .
برای این پریست ها و گلچین کردن آن ها زحمت بسیاری کشیده شده است .
آموزش پاکسازی پوست 02
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