Back

SARS-CoV-2 Spike evolution influences GBP and IFITM sensitivity

Mesner, D.; Reuschl, A.-K.; Whelan, M. V. X.; Bronzovich, T.; Haider, T.; Thorne, L. G.; Towers, G. J.; Jolly, C.

2022-05-17 microbiology
10.1101/2022.03.07.481785 bioRxiv
Show abstract

SARS-CoV-2 spike requires proteolytic processing for viral entry. The presence of a polybasic furin-cleavage site (FCS) in spike, and evolution towards an optimised FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmission. Here we show that interferon-inducible antiviral restriction factors Guanylate binding proteins (GBP) 2 and 5 interfere with furin-mediated cleavage of SARS-CoV-2 spike and inhibit the infectivity of early-lineage Wuhan-Hu-1, while VOCs Alpha and Delta have evolved to escape restriction. Strikingly, we find Omicron is unique amongst VOCs, being restricted by GBP2/5, and also IFITM1, 2 and 3. Replacing the spike S2 domain in Omicron with Delta shows S2 is the determinant of entry route and IFITM sensitivity. We conclude that VOC evolution under different selective pressures has influenced sensitivity to spike-targeting restriction factors, with Omicron selecting spike changes that not only mediate antibody escape, and altered tropism, but also sensitivity to innate immunity.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
Cell Host & Microbe
126 papers in training set
Top 0.1%
14.8%
2
PLOS Pathogens
● 820 papers in training set
Top 1%
12.4%
Similar papers in this journal
3
Cell Reports
○ 1498 papers in training set
Top 1%
11.7%
Similar papers in this journal
4
eLife
● 5828 papers in training set
Top 8%
11.7%
Similar papers in this journal
50% of probability mass above
5
mBio
● 833 papers in training set
Top 3%
6.1%
Similar papers in this journal
6
The EMBO Journal
○ 309 papers in training set
Top 0.6%
5.4%
7
Nature Communications
○ 5641 papers in training set
Top 28%
5.4%
8
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 17%
3.2%
9
Cell
○ 431 papers in training set
Top 3%
3.2%
10
Journal of Virology
● 499 papers in training set
Top 2%
2.7%
11
iScience
○ 1154 papers in training set
Top 12%
2.3%
12
Nature Microbiology
○ 155 papers in training set
Top 2%
2.1%
13
EMBO Reports
○ 263 papers in training set
Top 3%
1.9%
14
PLOS Biology
● 486 papers in training set
Top 5%
1.6%
15
Viruses
○ 332 papers in training set
Top 3%
1.5%
16
Current Biology
○ 665 papers in training set
Top 8%
1.1%
17
Frontiers in Cellular and Infection Microbiology
○ 109 papers in training set
Top 3%
1.1%
18
Journal of Experimental Medicine
● 119 papers in training set
Top 2%
1.1%
19
Virus Evolution
◐ 155 papers in training set
Top 1%
1.0%
20
Science Advances
● 1243 papers in training set
Top 31%
0.8%
21
mSphere
● 302 papers in training set
Top 8%
0.6%
22
Nature
○ 645 papers in training set
Top 12%
0.6%