#new paper in SARS-CoV-2 innate immunity
Pre-print in #bioRxiv
We found, SARS2 viral load and antiviral responses in nasal epithelium wane with advancing age, but Viral load alone is unlikely to explain differences in IFN induction observed.
biorxiv.org/content/biorxi…
thread/
Pre-print in #bioRxiv
We found, SARS2 viral load and antiviral responses in nasal epithelium wane with advancing age, but Viral load alone is unlikely to explain differences in IFN induction observed.
biorxiv.org/content/biorxi…
thread/
1/
We infected differentiated nasal epithelium cultures derived from healthy children (1-12 y/o), young adults (26-34 y/o) and older adults (56-62 y/o) with SARS2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host response
We infected differentiated nasal epithelium cultures derived from healthy children (1-12 y/o), young adults (26-34 y/o) and older adults (56-62 y/o) with SARS2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host response
2/
We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes
in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic
drug targets
We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes
in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic
drug targets
3/
viral transcript levels by qPCR were significantly lower in nasal epi from older adults than those of children
and young adults which was confirmed with RNA-seq with ~9% of reads from SARS2 in nasal epi from older adults compared to ~28% in children and young adults
viral transcript levels by qPCR were significantly lower in nasal epi from older adults than those of children
and young adults which was confirmed with RNA-seq with ~9% of reads from SARS2 in nasal epi from older adults compared to ~28% in children and young adults
4/
we followed the data, and found, Children and young adults nasal epi displayed robust, global proteomic and transcriptional responses to SARS2 infection, in
contrast, the transcriptional response to infection in older adult was almost completely absent
we followed the data, and found, Children and young adults nasal epi displayed robust, global proteomic and transcriptional responses to SARS2 infection, in
contrast, the transcriptional response to infection in older adult was almost completely absent
5/
Pathway enrichment analysis revealed similar responses in children and young adults nasal epi, with upregulation of interferon signalling, innate and adaptive immune response, apoptosis, cytokine, and inflammatory response pathways compared to older nasal epi
Pathway enrichment analysis revealed similar responses in children and young adults nasal epi, with upregulation of interferon signalling, innate and adaptive immune response, apoptosis, cytokine, and inflammatory response pathways compared to older nasal epi
6/
Relative of children and young, the IFN response was low in older with reduced expression of ISGs in nasal epi. RNA processing ISGs was also low in older adults. Young adult were the only age group with a significant upregulation of type I IFNs (IFN-β) in response to SARS2
Relative of children and young, the IFN response was low in older with reduced expression of ISGs in nasal epi. RNA processing ISGs was also low in older adults. Young adult were the only age group with a significant upregulation of type I IFNs (IFN-β) in response to SARS2
7/
We suggest that physiological differences in the expression of viral recognition and entry factors are poorly correlated to SARS2 viral load and do not explain differences in viral entry and replication associated with ageing.
We suggest that physiological differences in the expression of viral recognition and entry factors are poorly correlated to SARS2 viral load and do not explain differences in viral entry and replication associated with ageing.
8/
We postulate that intrinsic changes in gene expression that occur with ageing alter the epithelial microenvironment in a manner that primes the cell to launch a cytotoxic proinflammatory and IFN independent antiviral response.
We postulate that intrinsic changes in gene expression that occur with ageing alter the epithelial microenvironment in a manner that primes the cell to launch a cytotoxic proinflammatory and IFN independent antiviral response.
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