SARS-CoV-2 Mutations: B.1.1.7, B.1.351 & D614G Research

[Astronuc]

A potentially faster-spreading "sub-lineage" of the coronavirus Delta variant named AY.4.2 has been spotted by labs in at least 8 states, and health authorities in the United Kingdom say they are investigating a growing share of cases from this strain of the virus.

Labs in California, Florida, Maryland, Massachusetts, Nevada, North Carolina, Rhode Island and Washington state, plus the District of Columbia, have so far spotted at least one case of AY.4.2.

https://www.cbsnews.com/news/covid-delta-plus-variant-ay-4-2-states/

There are variants of the Covid-19 Coronavirus like the Delta variant. Then there are subvariants, which are variants of the variants. And AY.4.2 is a Delta subvariant that has now spread to at least 42 different countries, including the U.S., according to the latest World Health Organization (WHO) Weekly epidemiological update on Covid-19. This AY.4.2 takes the Delta variant and raises it three additional mutations, including two that affect the oh-so-important spike proteins that studs the surface of the virus. These mutations are called A222V and Y145H, . . .

https://www.forbes.com/sites/brucel...avirus-subvariant-has-spread-to-42-countries/

https://gvn.org/covid-19/delta-b-1-617-2/

https://www.bbc.com/news/health-58965650

https://www.cnbc.com/2021/10/21/the-delta-variant-has-a-mutation-what-we-know-so-far.html

I can't find any statement from WHO.int yet.

Repeating myself: What doesn't kill you, mutates and tries again, and again, . . .

 

[Ygggdrasil]

Regarding AY.4.2, data from England do suggest that AY.4.2 infections (purple on the graph below) continued to rise as delta infections (B.1.617.2, green on graph below) leveled off in Sep-Oct, which does suggest potential increased transmissibility of AY.4.2 over B.1.617.2:

https://covid19.sanger.ac.uk/lineages/raw

Unfortunately, it does not look like the US CDC variant tracking site tracks AY.4.2, as all of the delta lineages (except AY.1 and AY.2) are aggregated with B.1.617.2.

 

[Astronuc]

Some recent numbers on variants in California.

https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/COVID-19/COVID-Variants.aspx
low proportion of AY.1 and AY.2 in the State

 

[Ygggdrasil]

While most studies of COVID-19 variants have focused on mutations in the spike protein (which are important for determining the strength with which the virus binds to the ACE2 receptor in the cells it infects as well as binding to antibodies), here's a paper studying mutations to other proteins encoded by the SARS-CoV-2 virus. In particular, they find some mutations help to enhance the activity of Orf9b in helping the virus to evade the innate immune system.

Evolution of enhanced innate immune evasion by SARS-CoV-2
https://www.nature.com/articles/s41586-021-04352-y

Abstract:

Emergence of SARS-CoV-2 variants of concern (VOCs) suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on characterisation of spike changes in VOCs, mutations outside spike likely contribute to adaptation. Here we used unbiased abundance proteomics, phosphoproteomics, RNAseq and viral replication assays to show that isolates of the Alpha (B.1.1.7) variant3 more effectively suppress innate immune responses in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection4. The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.