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Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2
- Publication Year :
- 2021
- Publisher :
- Nature, 2021.
-
Abstract
- 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 infections1–3. 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.
- Subjects :
- Male
Transcription, Genetic
631/250/1619/554
medicine.disease_cause
DISEASE
Neutralization
Cohort Studies
13/1
631/250/2152/1566/1571
INFECTION
Coronaviridae
Asymptomatic Infections
Polymerase
Coronavirus
Multidisciplinary
biology
article
virus diseases
DNA-Directed RNA Polymerases
Multidisciplinary Sciences
13/31
Seroconversion
Cohort
Science & Technology - Other Topics
VIRUS
Female
82/75
HEALTH-CARE WORKERS
Antibody
ANTIBODY-RESPONSES
General Science & Technology
Health Personnel
13/106
IMMUNITY
Evolution, Molecular
Memory T Cells
In vivo
Multienzyme Complexes
medicine
Humans
EXPOSURE
631/326/596/4130
COVIDsortium Investigators
Cell Proliferation
PATHOGENS
Science & Technology
SARS-CoV-2
MEMORY
CORONAVIRUSES
COVID-19
Membrane Proteins
631/250/254
biology.organism_classification
Virology
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 00280836 and 14764687
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3d24ed2a1c420b2ed8ce5d2601a4f1d1