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Journal of translational medicine
01 07, 2021;19 (1): 32.

Transcriptome of nasopharyngeal samples from COVID-19 patients and a comparative analysis with other SARS-CoV-2 infection models reveal disparate host responses against SARS-CoV-2.

Abul Bashar Mir Md Khademul Islam, Md Abdullah-Al-Kamran Khan, Rasel Ahmed, Md Sabbir Hossain, Shah Md Tamim Kabir, Md Shahidul Islam, A M A M Zonaed Siddiki
Author Information
  1. Abul Bashar Mir Md Khademul Islam: Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, 1000, Bangladesh. khademul@du.ac.bd.
  2. Md Abdullah-Al-Kamran Khan: Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh.
  3. Rasel Ahmed: Basic and Applied Research On Jute Project, Bangladesh Jute Research Institute, Dhaka, Bangladesh.
  4. Md Sabbir Hossain: Basic and Applied Research On Jute Project, Bangladesh Jute Research Institute, Dhaka, Bangladesh.
  5. Shah Md Tamim Kabir: Basic and Applied Research On Jute Project, Bangladesh Jute Research Institute, Dhaka, Bangladesh.
  6. Md Shahidul Islam: Basic and Applied Research On Jute Project, Bangladesh Jute Research Institute, Dhaka, Bangladesh.
  7. A M A M Zonaed Siddiki: Department of Pathology and Parasitology, Chittagong Veterinary and Animal Sciences University (CVASU), Khulshi, Chittagong, Bangladesh.
PMID: 33413422 DOI: 10.1186/s12967-020-02695-0

Abstract

BACKGROUND: Although it is becoming evident that individual's immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems.
RESULTS: Unique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury.
CONCLUSIONS: Even though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.

Keywords

COVID-19 Genome variations Host transcriptional response Immune response Integrins SARS-CoV-2

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MeSH Term

Adult
Aged, 80 and over
COVID-19
Coronavirus 3C Proteases
Cytokines
Female
Genetic Variation
Host Microbial Interactions
Humans
Immunity, Innate
Integrins
Lung
Male
Middle Aged
Models, Immunological
Mutation, Missense
Nasopharynx
Pandemics
RNA-Seq
SARS-CoV-2
Signal Transduction
Transcriptome
Translational Research, Biomedical

Chemicals

Cytokines
Integrins
3C-like proteinase, SARS-CoV-2
Coronavirus 3C Proteases
Comparative Study Journal Article

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