Interferon resistance of emerging SARS-CoV-2 variants

被引:63
|
作者
Guo, Kejun [1 ]
Barrett, Bradley S. [1 ]
Morrison, James H. [1 ]
Mickens, Kaylee L. [1 ,2 ]
Vladar, Eszter K. [3 ]
Hasenkrug, Kim J. [4 ]
Poeschla, Eric M. [1 ,2 ]
Santiago, Mario L. [1 ,2 ]
机构
[1] Univ Colorado, Div Infect Dis, Dept Med, Anschutz Med Campus, Aurora, CO 80045 USA
[2] Univ Colorado, Dept Immunol & Microbiol, Anschutz Med Campus, Aurora, CO 80045 USA
[3] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Anschutz Med Campus, Aurora, CO 80045 USA
[4] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA
基金
美国国家卫生研究院;
关键词
SARS-CoV-2; COVID-19; interferons; innate immunity; variants of concern; I INTERFERON; ALPHA; IFN; LANDSCAPE; EMERGENCE; INFECTION; RESPONSES; SUBTYPES; LINEAGE; BETA;
D O I
10.1073/pnas.2203760119
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), B.1.617.2 (delta), and B.1.1.529 (omicron) lineages. Our data reveal that relative to ancestral isolates, SARS-CoV-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.
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页数:8
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