Videos capture lethal progress of COVID-19 virus

Date:
August 18, 2021
Source:
Yale University
Summary:
Video images capture for the first time in live animals the
inexorable spread of the COVID-19 virus, tracking the infection
as it moved from the noses of mice to the lungs and other organs
over the course of six days, in a new study.



FULL STORY ========================================================================== Video images capture for the first time in live animals the inexorable
spread of the COVID-19 virus, tracking the infection as it moved from
the noses of mice to the lungs and other organs over the course of six
days, in a new study led by researchers at Yale and Université
de Montréal.


========================================================================== While the images record the sometimes deadly march of SARS-CoV-2,
the virus that causes COVID-19, they also show how the introduction
of antibodies collected from humans who recovered from the virus can
prevent or treat infection.

However, the research also revealed that antibodies lacking the ability
to recruit killer immune system cells are less effective at combating infection.

The study, published online Aug. 18 in preproof form in the journal
Immunity, was led by Priti Kumar, Pradeep Uchil, and Walther Mothes,
all from Yale School of Medicine, as well as Andre's Finzi from Université de Montréal.

"For the first time, we were able to visualize the spread of the
SARS-CoV-2 in a living animal in real time, and importantly, the sites at
which antibodies need to exert effects to halt progression of infection,"
said Kumar, associate professor of infectious diseases at Yale School
of Medicine and a co- corresponding author of the paper.

For the study, co-lead authors Irfan Ullah, a Yale postdoctoral associate,
and Je're'mie Pre'vost, from Montreal, used bioluminescent tagging and
advanced microscopy to track the spread of the virus down to the level
of single cells.

In mice, the virus took a route that has become familiar to doctors
treating human patients, with high viral loads first appearing in nasal passages and then travelling quickly to lungs and eventually other
organs. The mice eventually died when virus reached the brain.

The researchers then used plasma from humans who had recovered from
COVID-19 to treat some of the infected mice, which halted the spread
of the virus even when administered as late as three days after
infection. When these antibodies were administered prior to infection
with the virus, researchers found, they prevented infection altogether.

"The live reporting of virus spread by imaging can be harnessed to rapidly discern whether treatments will work or not in as little as three to
five days, a crucial time-saving feature to develop countermeasures for
current and future pandemics" said Uchil, a research scientist in Mothes'
lab in the Department of Microbial Pathogenesis at Yale.

Researchers found that not all antibodies worked equally well, however.

Antibodies have two main roles. Neutralizing antibodies bind to and
prevent viruses from entering cells. Then, a second part of the antibody exhibits what are known as "effector" functions, which are necessary to
signal the immune system to attack and kill cells that are infected.

"Antibodies are polyfunctional molecules with several properties,"
Finzi said.

"In this study we show that their capacity to 'call for help' from other
cells in the immune system and eliminate infected cells is required to
provide optimal protection." Added Kumar: "We used to think neutralizing
the virus was enough to prevent infection, but antibodies have to be
present at the right time in the right place in the body and in right
amount. Without the effector function, the neutralizing activity alone
is not as effective." Other collaborators included Craig Wilen from Yale University, Mark Ladinsky and Pamela Bjorkman from California Institute of Technology, Leonidas Stamatatos and Andrew McGuire from Fred Hutchinson
Cancer Research Center, and Marzena Pazgier from Uniformed Services
University of the Health Sciences.

========================================================================== Story Source: Materials provided by Yale_University. Original written
by Bill Hathaway. Note: Content may be edited for style and length.


========================================================================== Related Multimedia:
* YouTube_video:_Tracking_COVID_progression_in_mice ========================================================================== Journal Reference:
1. Irfan Ullah, Je're'mie Pre'vost, Mark S. Ladinsky, Helen Stone,
Maolin
Lu, Sai Priya Anand, Guillaume Beaudoin-Bussie`res, Kelly Symmes,
Mehdi Benlarbi, Shilei Ding, Romain Gasser, Corby Fink, Yaozong
Chen, Alexandra Tauzin, Guillaume Goyette, Catherine Bourassa,
Halima Medjahed, Matthias Mack, Kunho Chung, Craig B. Wilen, Gregory
A. Dekaban, Jimmy D. Dikeakos, Emily A. Bruce, Daniel E. Kaufmann,
Leonidas Stamatatos, Andrew T.

McGuire, Jonathan Richard, Marzena Pazgier, Pamela J. Bjorkman,
Walther Mothes, Andre's Finzi, Priti Kumar, Pradeep D. Uchil. Live
Imaging of SARS-CoV-2 Infection in Mice Reveals that Neutralizing
Antibodies Require Fc Function for Optimal Efficacy. Immunity,
2021; DOI: 10.1016/ j.immuni.2021.08.015 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210818135213.htm

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