New Findings Challenge the Standard Understanding of COVID-19 Infection

Research conducted at UC Riverside has the potential to assist scientists in devising strategies to prevent the spread of COVID-19 among minks and various other species.

Some viruses have the ability to transfer across different speciesA species is a group of living organisms that share a set of common characteristics and are able to breed and produce fertile offspring. The concept of a species is important in biology as it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted one is the biological species concept, which defines a species as a group of organisms that can interbreed and produce viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>species. A notable instance of this is SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>SARS-CoV-2, the virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>virus responsible for COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>COVID-19. This virus can be transmitted from humans to minks, an agricultural species, and then potentially back to humans. This phenomenon, known as ‘spill back’, raises concerns because the virus may undergo mutations in minks and then return to humans in a more aggressive form. Instances of both transmission from humans to minks (spill over) and from minks to humans (spill back) have been documented in mink farms in both the United States and Europe.

To address these issues, a research team at the University of California, Riverside, has now studied zoonosis — the interspecies transmission of pathogens — in mink and found that TMPRSS2, an enzyme critical for viral fusion entry of SARS-CoV-2 in humans, is not functional in mink.

“We found mink lung cells are infected by the ‘endocytosis pathway,’ not the TMPRSS2 fusion pathway commonly observed in human cells,” said doctoral student Ann Song, first author of the research paper that appears in Frontiers in Microbiology. “Our findings show that SARS-CoV-2 entry is not the same in all mammals and emphasize the need for thorough investigations into viral entry mechanisms across different species.”

Song explained that viral fusion occurs when the membrane of the virus fuses with the plasmaPlasma is one of the four fundamental states of matter, along with solid, liquid, and gas. It is an ionized gas consisting of positive ions and free electrons. It was first described by chemist Irving Langmuir in the 1920s.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>plasma membrane of the host cell during infection. She said endocytosis is an essential process in which cells engulf external materials in small vesicles formed from their plasma membranes. SARS-CoV-2 can be taken up by host cells via endocytosis, she said.

Left: Prue Talbot (left) is seen with Ann Song, Right: Ann Song. Credit: Talbot Research Group, UC Riverside

“Our results show that the functional — or enzymatic — domain is missing in mink TMPRSS2,” she said. “We do not know why. We think the enzyme may have multiple functions. It can do something else in mink, but it does not play a role in SARS-CoV-2 fusion to host cells. As a result, targeting TMPRSS2 would not be helpful in preventing infection in mink. What is clear is that SARS-CoV-2 entry varies among different species and tissue types.”

Zoonosis as a Public Health Concern

Song said zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback. During the pandemic, hundreds of papers were published on COVID-19 in humans. Now that COVID-19 in humans is under better control, scientific attention is turning to zoonosis.

Lead author Prue Talbot, a professor of the graduate division in the Department of Molecular, Cell, and Systems Biology in whose lab Song works, said researchers should not underestimate the possibility of spillover and spillback of SARS-CoV-2 in other mammalian species.

“Deadly mutants can emerge from spillover/spillback events,” Talbot said. “As another example, many herds of deer, which are hunted by humans, are infected with SARS-CoV-2 and are thus potential sources of spillback.”

Talbot and Song were joined in the research by postdoctoral researcher Rattapol Phandthong. Next, the research team will work on the infectability of human embryos in pregnant women who have COVID-19.

To achieve their results, the researchers conducted their experiments using lung epithelial cells from mink.

Reference: “Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium” by Ann Song, Rattapol Phandthong and Prue Talbot, 27 October 2023, Frontiers in Microbiology.
DOI: 10.3389/fmicb.2023.1258975

The research was supported by the Tobacco-Related Disease Research Program of the University of California, California Institute for Regenerative Medicine, and UCR.