Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice.
Upper Respiratory Infection Drives Clinical Signs and Inflammatory Responses Following Heterologous Challenge of SARS-CoV-2 Variants of Concern in K18 Mice.
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DOI：
10.3390/v15040946
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发表时间：
2023-04-11
期刊：
影响因子：
--
通讯作者：
Jonsson CB
中科院分区：
文献类型：
--
作者：
Nichols JH;Williams EP;Parvathareddy J;Cao X;Kong Y;Fitzpatrick E;Webby RJ;Jonsson CB
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）的演变导致出现了几种令人担忧的变体（VOC），这些变体具有增加的免疫逃避和传播性。这促使研究评估感染或接种疫苗后早期菌株对每种新VOC的保护作用。我们假设，虽然NAb在预防感染和疾病方面发挥着重要作用，但异源再感染或挑战可能会在上呼吸道（URT）中站稳脚跟，并导致自限性病毒感染伴随炎症反应。为了验证这一假设，我们用SARS-CoV-2 USA-WA 1/2020（WA 1）感染K18-hACE 2小鼠，24天后，用WA 1、Alpha或Delta攻击。虽然在攻击前针对每种病毒的NAb滴度在所有群组中相似，但用α和δ攻击的小鼠在URT和较低RT（LRT）中显示体重减轻和促炎细胞因子上调。用WA 1攻击的小鼠显示出完全保护。我们注意到仅在用α和δ攻击的小鼠的URT中病毒RNA转录物水平增加。总之，我们的研究结果表明，自限性突破感染的α或δ在URT，这与临床症状和显着的炎症反应在小鼠。
The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response. To test this hypothesis, we infected K18-hACE2 mice with SARS-CoV-2 USA-WA1/2020 (WA1) and, after 24 days, challenged with WA1, Alpha, or Delta. While NAb titers against each virus were similar across all cohorts prior to challenge, the mice challenged with Alpha and Delta showed weight loss and upregulation of proinflammatory cytokines in the URT and lower RT (LRT). Mice challenged with WA1 showed complete protection. We noted increased levels of viral RNA transcripts only in the URT of mice challenged with Alpha and Delta. In conclusion, our results suggested self-limiting breakthrough infections of Alpha or Delta in the URT, which correlated with clinical signs and a significant inflammatory response in mice.
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DOI：
10.3390/v15030611
发表时间：
2023-02-23
期刊：
Viruses
影响因子：
--
作者：
Taylor MK;Williams EP;Xue Y;Jenjaroenpun P;Wongsurawat T;Smith AP;Smith AM;Parvathareddy J;Kong Y;Vogel P;Cao X;Reichard W;Spruill-Harrell B;Samarasinghe AE;Nookaew I;Fitzpatrick EA;Smith MD;Aranha M;Smith JC;Jonsson CB
通讯作者：
Jonsson CB
影响因子：
7.8
作者：
Ghazy RM;Ashmawy R;Hamdy NA;Elhadi YAM;Reyad OA;Elmalawany D;Almaghraby A;Shaaban R;Taha SHN
通讯作者：
Taha SHN
影响因子：
5
作者：
Bhattacharya M;Chatterjee S;Sharma AR;Agoramoorthy G;Chakraborty C
通讯作者：
Chakraborty C
DOI：
10.4269/ajtmh.20-1110
发表时间：
2020-12
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Kwon JS;Kim JY;Kim MC;Park SY;Kim BN;Bae S;Cha HH;Jung J;Kim MJ;Lee MJ;Choi SH;Chung JW;Shin EC;Kim SH
通讯作者：
Kim SH
影响因子：
17.1
作者：
Collier AY;Brown CM;McMahan KA;Yu J;Liu J;Jacob-Dolan C;Chandrashekar A;Tierney D;Ansel JL;Rowe M;Sellers D;Ahmad K;Aguayo R;Anioke T;Gardner S;Siamatu M;Bermudez-Rivera L;Hacker MR;Madoff LC;Barouch DH
通讯作者：
Barouch DH