SARS-CoV-2 variants remodel cellular landscapes
Viruses are obligate intracellular parasites, which means they rely on the cellular machinery within their hosts to replicate and assemble new virus particles. To achieve this, they have evolved sophisticated ways to hijack and alter cells while simultaneously overcoming an arsenal of immune defenses activated by viral infection.
Christian M眉nch, Sandra Ciesek and a team of scientists at Goethe University in Germany study how viruses can rewire their host cells. “We are keen on understanding cellular signaling responses to stress stimuli, such as viral infection,” M眉nch said.

Coronaviruses are a genus that infects many species, especially mammals and birds. Experts believe severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, crossed the species barrier and entered the human population to cause the COVID-19 pandemic. Since its detection in Wuhan, China, SARS-CoV-2 has mutated numerous times, resulting in the emergence of multiple variants. These variants may behave distinctly from one another, which can lead to reduced efficacy of antiviral treatments in patients.
The appearance of SARS-CoV-2 variants “definitely tickled our curiosity to examine host cellular antiviral responses,” M眉nch said. The team’s of these variants was published in the journal Molecular & Cellular Proteomics.
Led by Melinda Metzler and Rebecca Tharyan, the researchers began this investigation by infecting cells from lung tissue, the primary target of the virus in humans. They inoculated these lung cells with three viruses: the ancestral SARS-CoV-2 strain, the delta variant, and the omicron variant. The team discovered that the omicron variant replicated remarkably slower within these lung cells than the delta variant or ancestral strain. This was the first experimental indication of a unique cellular response to omicron infection.
Inside every cell are millions of proteins collectively known as the proteome. The scientists next sought to uncover what changes occurred in the proteomes of both the lung cell and the virus during infection.
“To study these time-resolved processes, we developed novel proteomics methods and set up a platform for cellular proteome profiles upon infection,” Tharyan said.
The researchers extracted the proteins from samples and then used mass spectrometry to identify and measure differences in protein quantities among cells infected with the three SARS-CoV-2 strains.
The proteomic analyses showed major cellular changes in all three infected samples, but cells infected by the omicron variant consistently exhibited alterations absent from the other strains. They detected the viral proteome to be significantly reduced in omicron-infected cells as well. Of particular interest was that the researchers also saw striking immunological delays in how cells responded to omicron.
Interferon, or IFN, proteins are a first line of defense against viruses. Omicron-infected cells took much longer to induce IFN proteins than the ancestral SARS-CoV-2 strain or delta variant, suggesting that the omicron virus was able to impede immune activation in these lung cells.
“It was intriguing to unravel such individuality in cellular responses at both proteome and molecular level,” Tharyan said.
Medical records indicate that compared to other variants, omicron infection results in milder cases of COVID-19. Despite its diminished disease burden, the omicron variant is significantly more contagious. Considering these facts, along with their findings on the lagging immune response to this particular variant, Tharyan and her colleagues concluded that in the case of omicron, “slow and steady wins the race.”
Enjoy reading 91影库Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from 91影库Today
Enter your email address, and we鈥檒l send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

Hope for a cure hangs on research
Amid drastic proposed cuts to biomedical research, rare disease families like Hailey Adkisson鈥檚 fight for survival and hope. Without funding, science can鈥檛 鈥渃atch up鈥 to help the patients who need it most.

Before we鈥檝e lost what we can鈥檛 rebuild: Hope for prion disease
Sonia Vallabh and Eric Minikel, a husband-and-wife team racing to cure prion disease, helped develop ION717, an antisense oligonucleotide treatment now in clinical trials. Their mission is personal 鈥 and just getting started.

Defeating deletions and duplications
Promising therapeutics for chromosome 15 rare neurodevelopmental disorders, including Angelman syndrome, Dup15q syndrome and Prader鈥揥illi syndrome.

Using 'nature鈥檚 mistakes' as a window into Lafora disease
After years of heartbreak, Lafora disease families are fueling glycogen storage research breakthroughs, helping develop therapies that may treat not only Lafora but other related neurological disorders.

Cracking cancer鈥檚 code through functional connections
A machine learning鈥揹erived protein cofunction network is transforming how scientists understand and uncover relationships between proteins in cancer.

Gaze into the proteomics crystal ball
The 15th International Symposium on Proteomics in the Life Sciences symposium will be held August 17鈥21 in Cambridge, Massachusetts.