Skip to main content

Enhanced #RNA #replication and #pathogenesis in recent #SARS-CoV-2 #variants harboring the L260F mutation in NSP6

Image
By G.M.

Abstract

The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape. Apart from extensive evolution in the Spike protein, non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated, suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replication. NSP6 emerged as a hotspot with a distinct L260F mutation independently arising in the BQ.1.1 and XBB.1.16 variants. Using mutant and revertant NSP6 viral clones, the L260F mutation was validated to enhance viral replication in cells and increase pathogenesis in mice. Notably, this mutation enhanced host lipid droplet consumption by NSP6 without impacting its known ER-zippering function or double-membrane vesicle morphology. Collectively, a systematic analysis of RNA replication of recent Omicron variants defined NSP6 key role in viral RNA replication that provides insight into evolutionary trajectories of recent variants with possible therapeutic implications.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.30.628795v1?rss=1

_____

Labels

Labels:

Comments

Post a Comment

Popular posts from this blog

#USA, APHIS Confirms {Avian #Influenza #H5N1} #D11 #Genotype in Dairy #Cattle in #Nevada

By G.M.
On January 31, 2025, the USDA Animal and Plant Health Inspection Service (APHIS) National Veterinary Services Laboratories (NVSL) confirmed by whole genome sequence the first detection of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b, genotype D1.1 in dairy cattle .  This confirmation was a result of State tracing and investigation, following an initial detection on silo testing under the USDA’s National Milk Testing Strategy (NMTS) in Nevada.  USDA APHIS continues to work with the Nevada Department of Agriculture by conducting additional on-farm investigation, testing, and gathering additional epidemiological information to better understand this detection and limit further disease spread.  This is the first detection of this virus genotype in dairy cattle (all previous detections in dairy cattle have been HPAI H5N1 clade 2.3.4.4b, genotype B3.13 ).  Genotype D1.1 represents the predominant genotype in the North American flyways this past fall an...
Post a Comment
Read more »

#USA, After #Birdflu Detected in Local #Cat, County #Health Officials Say #Pet Owners Should Contact Veterinarian When Their Pets are Sick

By G.M.
Redwood City — State veterinary and health officials have confirmed a case of H5N1 (bird flu) in a domestic stray cat in San Mateo County.  The infection, which is not related to the recent instance of bird flu in a backyard flock , was found in a stray cat in Half Moon Bay that had been taken in by a family .  When it showed symptoms, they took it to Peninsula Humane Society, whose veterinarians examined it and requested testing. Lab results confirmed H5N1.  It is not known how the cat was infected and it was euthanized due to its condition. Cats may be exposed to bird flu by consuming infected bird , being in environments contaminated with the virus and consuming unpasteurized milk from infected cows or raw food. Inside domestic animals, such as cats and dogs, that go outside are also at risk of infection.​​​​​​​ According to the Centers for Disease Control and Prevention, the risk of cats spreading H5N1 to people is extremely low, though it is possible for cats to spre...
Post a Comment
Read more »

Young #boy in #Cambodia contracts #H5N1 #birdflu

By G.M.
PHNOM PENH, March 23 (Xinhua) -- A three-year-and-six-month boy from northeast Cambodia's Kratie province has been confirmed for H5N1 human avian influenza , raising the number of cases to three so far this year , said a Ministry of Health's statement on Sunday. The boy had been brought to the hospital in a critical condition with fever, cough, and dyspnea , it said, adding that he is receiving medical treatment with the utmost care from a team of doctors. "According to queries, the patient's family raised chickens and about five chickens had died , as some others were sick, and his family members cooked the dead poultry for food," the statement said. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the patient in order to prevent an outbreak in the community, it added. Among the three human cases of H5N1 so far this year , two had died, and all patients reportedly had a h...
Post a Comment
Read more »