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Capturing Viral Shedding in Action

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Credit: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT

You’ve probably seen some amazing high-resolution images of SARS-CoV-2, the novel coronavirus that causes COVID-19, on television and the web. What you might not know is that many of these images, including the ones shown here, were produced at Rocky Mountain Laboratories (RML), a part of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) that’s located in the small Montana town of Hamilton.

The head of RML’s Electron Microscopy Unit, Elizabeth Fischer, was the researcher who took this portrait of SARS-CoV-2. For more than 25 years, Fischer has snapped stunning images of dangerous viruses and microbes, including some remarkable shots of the deadly Ebola virus. She also took some of the first pictures of the coronavirus that causes Middle East respiratory syndrome (MERS), which arose from camels and continues to circulate at low levels in people.

The NIAID facility uses a variety of microscopy techniques, including state-of-the-art cryo-electron microscopy (cryo-EM). But the eye-catching image you see here was taken with a classic scanning electron microscope (SEM).

SEM enables visualization of particles, including viruses, that are too small to be seen with traditional light microscopy. It does so by focusing electrons, instead of light, into a beam that scans the surface of a sample that’s first been dehydrated, chemically preserved, and then coated with a thin layer of metal. As electrons bounce off the sample’s surface, microscopists such as Fischer are able to capture its precise topology. The result is a gray-scale micrograph like the one you see above on the left. To make the image easier to interpret, Fischer hands the originals off to RML’s Visual Medical Arts Department, which uses colorization to make key features pop like they do in the image on the right.

So, what exactly are you seeing in this image? The orange-brown folds and protrusions are part of the surface of a single cell that’s been infected with SARS-CoV-2. This particular cell comes from a commonly studied primate kidney epithelial cell line. The small, blue spheres emerging from the cell surface are SARS-CoV-2 particles.

This picture is quite literally a snapshot of viral shedding, a process in which viral particles are released from a dying cell. This image gives us a window into how devastatingly effective SARS-CoV-2 appears to be at co-opting a host’s cellular machinery: just one infected cell is capable of releasing thousands of new virus particles that can, in turn, be transmitted to others.

While capturing a fixed sample on the microscope is fairly straightforward for a pro like Fischer, developing a sample like this one involves plenty of behind-the-scenes trial and error by NIAID investigators. As you might imagine, to see the moment that viruses emerge from an infected cell, you have to get the timing just right.

By capturing many shots of the coronavirus using the arsenal of microscopes available at RML and elsewhere, researchers are learning more every day about how SARS-CoV-2 enters a cell, moves inside it, and then emerges to infect other cells. In addition to advancing scientific knowledge, Fischer notes that images like these also hold the remarkable power to make an invisible enemy visible to the world at large.

Making SARS-CoV-2 tangible helps to demystify the challenges that all of us now face as a result of the COVID-19 pandemic. The hope is it will encourage each and every one of us to do our part to fight it, whether that means digging into the research, working on the front lines, or staying at home to prevent transmission and flatten the curve. And, if you could use some additional inspiration, don’t miss the NIAID’s image gallery on Flickr, which includes some of Fischer’s finest work.

Links:

Coronavirus (COVID-19) (NIH)

Rocky Mountain Laboratories (National Institute of Allergy and Infectious Diseases/NIH)

Elizabeth Fischer (National Institute of Allergy and Infectious Diseases/NIH)

NIH Support: National Institute of Allergy and Infectious Diseases

10 Comments

  • Dinesh Patel says:

    Thank you
    Amazing work
    Science at its best
    Nature and the creator of this infinite earth needs to be respected and prayed for their blessings
    Creator should be creator and not destructor but perhaps the almighty is stimulating us to learn and work together for humanity and Prakriti …

  • Elizabeth Newberry says:

    The intricacy of nature is of great wonder. Understanding how these things work is fundamental to being able to find ways to combat the mutations and new viruses that threaten life. What a task you and the scientific community have ahead of you in order to find scientific ways to mitigate this awful virus that has infected our lives. Thank you for your dedication.

  • Kristie Jackson says:

    Dr. Collins, my husband and I were both C.S. Lewis Institute fellows and have respect not only for your work, but your faith. I am increasingly concerned that there is a lack of transparency about the reality of the coronavirus. You initially stated, along with others, that the goal of lockdowns was to flatten the curve to not overwhelm the healthcare system. It feels like the goal has shifted. Is that a fair statement? I also am perplexed by how many disingenuous comments are made about when the economy can re-open. “Taking every precaution” and “ensuring safety” are not reasonable standards. Can you put voice to what would be an honest consideration? Why is there such reluctance to openly and thoughtfully discuss the tremendous unintended consequences of taking the action that we have?

    As an aside I also read The Atlantic piece a few weeks back that talked about your relationship with Hichens. I was so inspired by how you modeled loving others through that dear friendship. What a sad reality that those kinds of friendships seem so strikingly rare.

  • DR. SAUMYA PANDEY, PH.D. says:

    A thought-provoking and scientifically fascinating article highlight; elegantly presented viral-shedding SARS-Covid-2 particles’ membrane-shedding, virulence, replication, transmission added to my scientific knowledge.
    It would be worthwhile to develop future public health-oriented global cost-effective research models for demystifying the intricacies involved in respiratory-distress associated with Covid-19 shedding, including membrane-spatiotemporal dynamics-ion-channel physiology coupled with lipid-rafts-rich viral-laden memebrane fractions and patients’-derived clinical tissues for stratifying Covid-19/SARS-seropositive cases borderline and symptomatic and further performing large-sample size based statistically-powered multicentric genetic-association/pharmacogenetic epidemiology studies with pooled samples from genetically heterogeneous populations of North American and Asian Indian ethnically disparate populations.
    Viral-shedding, transmembrane signaling and therapeutics deserve timely collaborative research endeavors for eventually diminishing and eradicating the global pandemic Covid-19.

  • Madeline M. Athanas says:

    As a scientist myself, I’m wondering what the magnification is? Posting that information helps give people an appreciation for just how small this virus is.
    The pics are astonishing!! Thank you.

  • Vernon McAlister says:

    Never let a good pandemic go to waste, this is a time of great teaching, this taught us many things about cellular life, this virus
    teaches us exactly how to take future medicine many leaps and bounds forward, it so far taught us that the ACE2 receptor can be manipulated to lower the immune system, from this we can develop hundreds of new medicines to lower people’s immunity
    when it is raging, many hundreds of maladies now possibly can be cured just from this one discovery along.
    It also taught us how to open the cell allowing specific medicinal fixes into the cell and also how to replicate parts of the RNA
    that we wish to, in the future just these few teachings alone will eventually save as many as are being sacrificed today.

    Lessons of value most often come with sacrifices.

  • Bongani Lala says:

    We all have to learn and find a way to work together. in times like these we see that together we stand and divided we fall

    • Vernon McAlister says:

      I did realize all of it, and realized all of the dedicated work involved in both aspects, thank you guys for sharing such dramatic
      image captures for those of us who do not have access to a 3D electron microscope. Bless you in all further efforts.

  • Pam Steele says:

    When do the coronal “spikes” appear in the lifecycle of the virus? Obviously to infect other cells and in transmission mode to infect other hosts.. But what if they don’t appear? Can they stay within the human host in stealth mode? The “spikes” remaining as “buds” as shown in this remarkable image. After all the virus is “cloaked” in human cell walls, so how would the immune system recognise it from the host’s cells? Is it only when the “spikes” appear that it is recognizable as foreign protein? I believe that the “spikes” are glyco-proteins, the proteins being produced by the DNA of the virus. Can these proteins mutate? In such a huge number of hosts, that seems likely, just on a statistical level. The human race is the perfect laboratory and host for this virus.

    Also is the immune system triggered by remnants of the viral RNA in the damaged host cell as well as the “spikes”? Will the immune system memorize this invasion long enough for the next activation of the virus? No one knows yet, I appreciate this. But these are questions to which you may know the answer or want to know the answer, especially in developing a vaccine.

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