Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection
- Translational Health Science and Technology Institute, India
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.
Data availability
All data pertaining to the manuscript are made available in Dryad.
-
Immunological and cardio-vascular pathologies associated with SARS-CoV2 infection in golden Syrian hamsters.Dryad Digital Repository, doi: 10.5061/dryad.vhhmgqnvt.
Article and author information
Author details
Funding
THSTI core
- Amit Awasthi
Translational Research Program
- Amit Awasthi
DST-SERB
- Amit Awasthi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the institutional animal ethics committee (IAEC) guidelines and all the protocols and procedures involved in the study were approved (IAEC approval number: IAEC/THSTI/94). The experimental procedures on animals were followed in strict accordance with the animal handling and usage guidelines by the IAEC and small animal facility, THSTI. Infection through intranasal route was performed under anesthesia to minimize pain.
Human subjects: Human plasma samples were collected according to the recommended guidelines of the Institutional Ethics Committee (Human Research) of THSTI and ESIC Hospital, Faridabad (Letter Ref No: THS 1.8.1/ (97) dated 07th July 2020). Human blood samples were collected from COVID-19 patients and healthy individuals after the written informed consent. Individuals were enrolled in this study based on the inclusion/exclusion criteria prescribed by the Institutional Ethics Committee (Human Research) of THSTI.
Copyright
© 2022, Rizvi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,770
- views
-
- 514
- downloads
-
- 56
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection
eLife 11:e73522.
https://doi.org/10.7554/eLife.73522
Further reading
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
HIV and simian immunodeficiency virus (SIV) infections are known for impaired neutralizing antibody (NAb) responses. While sequential virus–host B cell interaction appears to be basally required for NAb induction, driver molecular signatures predisposing to NAb induction still remain largely unknown. Here we describe SIV-specific NAb induction following a virus–host interplay decreasing aberrant viral drive of phosphoinositide 3-kinase (PI3K). Screening of seventy difficult-to-neutralize SIVmac239-infected macaques found nine NAb-inducing animals, with seven selecting for a specific CD8+ T-cell escape mutation in viral nef before NAb induction. This Nef-G63E mutation reduced excess Nef interaction-mediated drive of B-cell maturation-limiting PI3K/mammalian target of rapamycin complex 2 (mTORC2). In vivo imaging cytometry depicted preferential Nef perturbation of cognate Envelope-specific B cells, suggestive of polarized contact-dependent Nef transfer and corroborating cognate B-cell maturation post-mutant selection up to NAb induction. Results collectively exemplify a NAb induction pattern extrinsically reciprocal to human PI3K gain-of-function antibody-dysregulating disease and indicate that harnessing the PI3K/mTORC2 axis may facilitate NAb induction against difficult-to-neutralize viruses including HIV/SIV.
-
- Evolutionary Biology
- Microbiology and Infectious Disease
Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated ‘mutational fitness’ of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.
