Asset Details
Do you wish to reserve the book?
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Do you wish to request the book?
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
2022
Overview
Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections
1
–
3
. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs.
4
–
11
), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC)
12
,
13
, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in
IFI27
, a robust early innate signature of SARS-CoV-2 (ref.
14
), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging
Coronaviridae
.
Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/31
/ 82/75
/ COVID-19
/ DNA-Directed RNA Polymerases - immunology
/ DNA-Directed RNA Polymerases - metabolism
/ Epitopes
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Membrane Proteins - immunology
/ Multienzyme Complexes - immunology
/ Peptides
/ Proteins
/ SARS-CoV-2 - growth & development
/ Science
/ Severe acute respiratory syndrome coronavirus 2
