The cellular response that protects pigs from COVID-19
Research could lead to new treatments in humans

Date:
January 20, 2022
Source:
Iowa State University
Summary:
Studies since the start of the pandemic have noted that pigs exposed
to the coronavirus don't show clinical signs of disease nor do
they transmit the virus to other animals. Scientists have uncovered
important clues that shed light on why pigs don't get sick, and the
discovery could lead to better treatments for COVID-19 in humans.



FULL STORY ==========================================================================
Iowa State University scientists may have uncovered an important clue that sheds light on why pigs don't get sick when exposed to the coronavirus.


========================================================================== Studies since the start of the pandemic have noted that pigs can be
infected by the virus if exposed to high doses, but the infection
is self-limited and pigs don't show clinical signs of disease nor do
they transmit the virus to other animals. So Rahul Nelli, a research
assistant professor of veterinary diagnostic and production animal
medicine, and Luis Gimenez-Lirola, an associate professor of veterinary diagnostic and production animal medicine, set out to find out why in a
newly published study in the academic journal Cell Death Discovery. What
they found could lead to new ways to treat humans who contract COVID-19,
the disease that results from infection by the virus SARS- CoV-2, said
Nelli and Gimenez-Lirola.

Nelli and Gimenez-Lirola have studied how coronaviruses affect pigs
for years.

They've developed models that allow them to study in detail how
viruses infect pigs and pig cells and how the cells respond to fight
the infection. For the latest experiments, they introduced the virus to cultured porcine and human respiratory epithelial cells, which line most
of the respiratory tract. They found the pig cells underwent apoptosis,
or controlled cell death, in response to infection at a higher rate than
human epithelial cells.

"When we looked under the microscope there was an interesting phenomenon
going on inside the cells," Nelli said. "The nuclei of the infected
pig cells were starting to shred into fragments but not uninfected pig
cells." That shredding of the nucleus is a telltale sign of apoptosis,
which may be a key in helping pigs avoid symptoms after exposure to
SARS-CoV-2. Triggering apoptosis early in the infection essentially
causes minimal tissue damage and confines viral replication, thus
limiting severe illness. Human cells can undergo apoptosis in response
to coronavirus infection as well, but the study found human cells do so
much less frequently than porcine cells. Pig cells are roughly 100 times
more likely to undergo apoptosis than human cells, according to the study.

Human cells are more likely to go through necrosis, another form of
cell death that's less controlled than apoptosis. During necrosis,
the contents of a cell release into the surrounding space, provoking a
strong hyperimmune response that isn't triggered during apoptosis.

The researchers surmise that a wide-scale apoptosis response is helpful
for avoiding disease because it disposes of infected cells quickly
without the immune system overreacting, while wide-scale necrosis and
the resulting hyperimmune response is less favorable to host cells.

"We don't want to over-conclude, but this response is probably something intrinsic to the pig immune system that is innate and not acquired,"
Giminez- Lirola said. "The idea is to kill the virus subtly but
fast enough so there's not an excessive immune response triggered."
The researchers said further study could lead to therapies designed
to trigger apoptosis in human cells, allowing people infected with the coronavirus to avoid severe symptoms.

The next step for the ISU research team is to identify all the genes
activated during the infectious process and compare them with other
animal species in which those genes are present. That could give them
further clues about how and why other animals, such as deer, can carry
the virus without suffering symptoms of disease.

In addition to Nelli and Gimenez-Lirola, the research team included
Kruttika Phadke, Gino Castillo, Lu Yen and Bryan Bellaire at Iowa
State. Amy Saunders, Rolf Rauh and William Nelson of Maryland-based
Tetracore, Inc., are also listed as co-authors of the study.

========================================================================== Story Source: Materials provided by Iowa_State_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Rahul K. Nelli, Kruttika-S Phadke, Gino Castillo, Lu Yen, Amy
Saunders,
Rolf Rauh, William Nelson, Bryan H. Bellaire, Luis
G. Gime'nez-Lirola.

Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-
2 replication in porcine primary respiratory epithelial cells in
contrast to human cells. Cell Death Discovery, 2021; 7 (1) DOI:
10.1038/s41420- 021-00781-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220120125443.htm

--- up 6 weeks, 5 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)