New Dog Coronavirus Jumps to Humans, With a Protein Shift
By CORNELL UNIVERSITY
.webp)
Cornell scientists have identified a shift that occurs in canine
coronavirus that points to a possible pattern of change found in other
coronaviruses and which may provide clues to how they transmit to humans from
animals.
A new canine coronavirus was first identified in two Malaysian
human patients who developed pneumonia in 2017-18. A group of other
scientists isolated the canine
coronavirus, sequenced it, and published their findings in
2021.
A team led by Cornell and Temple University scientists has now
uncovered a pattern that appears in the canine coronavirus spike protein’s
terminus – the portion of the virus that allows entrance into a host cell: The
virus switches from infecting both the intestines and the respiratory system of
the animal host to exclusively infecting the respiratory system of the human
host.
The researchers identified a change in the terminus – known as the N terminus – a region of the molecule with alterations also detected in another coronavirus, which jumped from bats to humans, where it causes a common cold.
The paper, “Recent Zoonotic Spillover and Tropism Shift of a
Canine Coronavirus is Associated with Relaxed Selection and Putative Loss of
Function in NTD Subdomain of Spike Protein,” was published on April 21, 2022,
in the MDPI journal Viruses.
“This study identifies some of the molecular mechanisms underlying
a host shift from dog coronavirus to a new human host, that may also be
important in the circulation of a new human coronavirus that we previously
didn’t know about,” said Michael Stanhope, professor of public and ecosystem
health in the College of Veterinary Medicine. First author Jordan Zehr is a
doctoral student in the lab of co-author Sergei Kosakovsky Pond, professor of
biology in the Institute for Genomics and Evolutionary Medicine at Temple
University.
In the study, the researchers used state-of-the-art molecular
evolution tools developed in Pond’s lab to assess how pressures from natural
selection may have influenced the canine coronavirus’ evolution.
In humans, the main receptor that the Alphacoronavirus (the genus
to which canine coronavirus is classified) spike protein binds with in order to
enter a human cell is called APN, but there are also co-receptors. One of these
co-receptors is sialic acid, which is found in
gastrointestinal cells in a variety of mammals. The researchers identified a
region of the spike protein in the N-terminus called the O-domain, which is
known for binding with sialic acid. In the analysis of the canine coronavirus
found in the Malaysian patients, parts of the O-domain were changing in unique
ways.
The canine coronavirus found in the Malaysian patients appeared to
be in the process of losing its O-domain – but not completely. “But it has a
molecular evolution history that suggests that the sialic acid binding region
is no longer doing the same job,” Stanhope said. The researchers found evidence
of “relaxed evolution,” where the pressures of natural selection become
reduced, which facilitated the shift.
The researchers compared this shift and loss of the O-domain to
other related coronaviruses. One, called transmissible gastroenteritis virus
(TGEV), infects pigs and causes respiratory and intestinal disease. A variant
of this pig virus, called porcine respiratory coronavirus, is almost identical
to TGEV, but it has lost its O-domain and is entirely a respiratory pathogen.
Similarly, a coronavirus known to cause common human colds originated in bats
as a gastrointestinal virus, lost its O-domain, and jumped to a human host as a
respiratory virus.
“So this is a pattern that seems to be repeating itself in
coronavirus evolution and in particular in coronavirus evolution associated
with these tropism shifts, where we go from a gastrointestinal infection
originally and then jumping to an alternate host, where it’s now respiratory,”
Stanhope said.
The same variant of canine coronavirus found in Malaysia was also
reported in 2021 in a few people in Haiti, who also had respiratory illness.
More study is needed to understand if the viral shifts and jumps to humans
occurred spontaneously in different parts of the world or if this coronavirus,
which would represent the eighth known human coronavirus, has been circulating
for perhaps many decades in the human population without detection, Stanhope
said.
The N-terminus domain of SARS-CoV2, which causes COVID-19, is receiving increasing attention from
researchers, and this study provides additional rationale to focus on this
specific area of the molecule.
Reference: ” Recent Zoonotic Spillover and Tropism Shift of a Canine
Coronavirus Is Associated with Relaxed Selection and Putative Loss of Function
in NTD Subdomain of Spike Protein” by Jordan D. Zehr, Sergei L. Kosakovsky
Pond, Darren P. Martin, Kristina Ceres, Gary R. Whittaker, Jean K. Millet,
Laura B. Goodman and Michael J. Stanhope, 21 April 2022, Viruses.
DOI: 10.3390/v14050853
The study is funded by the U.S. Food and Drug Administration’s Veterinary Laboratory Investigation and Response Network and the National Institutes of Health.
