Friday, November 13, 2020

Study: SARS-CoV-2 D614G Variant Exhibits Efficient Replication Ex Vivo and Transmission in Vivo


 

#15,558

We've a new study - published yesterday in the Journal Science - that seems to confirm previous suspicions that a mutation (D614G) - which appeared in the SARS-CoV-2 virus after it arrived in Europe last January - enhances the virus's transmissibility and replication rate. 

All viruses mutate, some very slowly, and others - like HIV or Influenza - very rapidly. Most mutations convey no biological advantage to the virus, and many are actually detrimental. Only a few are apt to `improve' the fitness of the virus. 
 
But, when viruses make trillions of copies of themselves, every once in awhile a more biologically `fit' virus will emerge; one that can compete against its parental strain, and sometimes even supplant it. And in this case, over the past 10 months this D614G variant has become dominant in most of the world, at least outside of China and some parts of Asia. 

While many scientists (and public officials) initially downplayed the idea, starting last May we began to see a number of pre-print studies (see More COVID-19 (SARS-CoV-2) Mutation Reports) that identified a specific mutation (D614G) in the spike protein that appeared to enhance its transmissibility.

Among them, this one from the Los Alamos National Laboratory, which describes this new, now dominant `European' strain of COVID-19.
Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2
B Korber,  WM Fischer,   S Gnanakaran, H Yoon,   J Theiler, W Abfalterer,   B Foley, EE Giorgi,   T Bhattacharya, MD Parker, DG Partridge, CM Evans,  TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group,  CC LaBranche, DC Montefiori
doi: https://doi.org/10.1101/2020.04.29.069054
Another study from the University College London, called Emergence of genomic diversity and recurrent mutations in SARS-CoV-2, `. . . . identified close to 200 recurrent genetic mutations in the virus, highlighting how it may be adapting and evolving to its human hosts.' 

While this D614G variant appears more easily transmitted than its parental strain, it does not seem to cause any worse illness in humans. It may, however, partially explain why Western nations have had less success in containing COVID-19 than has China, Taiwan, and Japan.

This latest report by researchers at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison, confirms (using animal studies) that this variant is not only more infectious, it replicates 10 times faster than its ancestral strain. 

While a more transmissible virus is never a good thing, the news isn't all bad, as the researchers suggest this variant may be slightly more susceptible to vaccines currently under development.

First a link and the Abstract from the study (full text available at link), followed by a link and a few brief excerpts from a press release from the University of North Carolina at Chapel Hill.  

You'll want to follow the links and read both in their entirety. 

REPORT
Yixuan J. Hou1,*, Shiho Chiba2,*, Peter Halfmann2, Camille Ehre3, Makoto Kuroda2, Kenneth H. Dinnon III4, Sarah R. Leist1, Alexandra Schäfer1, Noriko Nakajima5, Kenta Takahashi5, Rhianna E. Lee3, Teresa M. Mascenik3, Rachel Graham1, Caitlin E. Edwards1, Longping V. Tse1, Kenichi Okuda3,  Alena J. Markmann6, Luther Bartelt6, Aravinda de Silva4, David M. Margolis4,6, Richard C. Boucher3,  Tadaki Suzuki5, Lisa E. Gralinski1, Yoshihiro Kawaoka2,7,, Ralph S. Baric1,4,
Science 12 Nov 2020:
 
DOI: 10.1126/science.abe8499

Abstract
The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

          (Continue . . .)

 

Common SARS-CoV-2 mutation may make COVID-19 more susceptible to a vaccine

Mutation is not expected to interfere with effectiveness of vaccines under development

Date:
November 12, 2020
Source:
University of North Carolina at Chapel Hill
Summary:
A common strain of coronavirus has mutated to help it spread quickly, but the spike mutation may make SARS-CoV-2 more susceptible to vaccines under development, according to a new study.
(Excerpt)

A new study published in Science confirms that SARS-CoV-2 has mutated in a way that's enabled it to spread quickly around the world, but the spike mutation may also make the virus more susceptible to a vaccine.

The new strain of coronavirus, called D614G, emerged in Europe and has become the most common in the world. Research at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison shows the D614G strain replicates faster and is more transmissible than the virus, originating in China, that spread in the beginning of the pandemic.

There were bright spots in the study findings: While the D614G strain spreads faster, in animal studies it was not associated with more severe disease, and the strain is slightly more sensitive to neutralization by antibody drugs.

(SNIP) 

The researchers also examined the pathology of the two coronavirus strains. Once hamsters were infected, they presented essentially the same viral load and symptoms. (The hamsters with the mutated strain lost slightly more weight while sick.) This suggests that while the mutant virus is much better at infecting hosts, it doesn't cause significantly worse illness.

Researchers caution that the pathology results may not hold true in human studies.

"SARS-CoV-2 is an entirely new human pathogen and its evolution in human populations is hard to predict," Baric said. "New variants are continually emerging, like the recently discovered mink SARS-CoV-2 cluster 5 variant in Denmark that also encodes D614G.

"To maximally protect public health, we must continue to track and understand the consequences of these new mutations on disease severity, transmission, host range and vulnerability to vaccine-induced immunity."