Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques DOI Creative Commons
Taehwan Oh, Green Kim, Seung Ho Baek

и другие.

Journal of Medical Virology, Год журнала: 2023, Номер 95(6)

Опубликована: Июнь 1, 2023

Abstract Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to virus's heterogeneous distribution within complex tissue structure. Here, we revealed spatial transcriptomic profiles of microstructures at SARS‐CoV‐2 infection site in nine cynomolgus macaques upon inoculation with Delta and variants. Delta‐ Omicron‐infected lungs had upregulation genes involved inflammation, cytokine response, complement, cell damage, proliferation, differentiation pathways. Depending on (alveoli, bronchioles, blood vessels), there were differences types significantly upregulated each pathway. Notably, a limited number damage differentially expressed between bronchioles Omicron‐infection groups. These results indicated that despite significant antigenic shift SARS‐CoV‐2, host mechanisms induced by relatively consistent, transcriptional observed only large airways. This study may aid understanding pathogenesis developing clinical strategy addressing dysregulation identifying potential biomarkers during

Язык: Английский

SARS-CoV-2 variant biology: immune escape, transmission and fitness DOI Creative Commons
Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne

и другие.

Nature Reviews Microbiology, Год журнала: 2023, Номер unknown

Опубликована: Янв. 18, 2023

In late 2020, after circulating for almost a year in the human population, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited major step change its adaptation to humans. These highly mutated forms of SARS-CoV-2 had enhanced rates transmission relative previous variants and were termed 'variants concern' (VOCs). Designated Alpha, Beta, Gamma, Delta Omicron, VOCs emerged independently from one another, turn each rapidly became dominant, regionally or globally, outcompeting variants. The success VOC previously dominant variant was enabled by altered intrinsic functional properties virus and, various degrees, changes antigenicity conferring ability evade primed immune response. increased fitness associated with is result complex interplay biology context changing immunity due both vaccination prior infection. this Review, we summarize literature on transmissibility variants, role mutations at furin spike cleavage site non-spike proteins, potential importance recombination success, evolution T cells, innate population immunity. shows complicated relationship among antigenicity, virulence, which has unpredictable implications future trajectory disease burden COVID-19.

Язык: Английский

Процитировано

989
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells DOI Creative Commons
Nicolas Huot, Cyril Planchais,

Pierre Rosenbaum

и другие.

Nature Immunology, Год журнала: 2023, Номер 24(12), С. 2068 - 2079

Опубликована: Ноя. 2, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used model of viral infection macaques to address whether SARS-CoV-2 persists the body and which mechanisms regulate its persistence. Replication-competent virus was detected bronchioalveolar lavage (BAL) macrophages beyond 6 months Viral propagation BAL occurred from cell inhibited by interferon-γ (IFN-γ). IFN-γ production strongest NKG2r+CD8+ T cells NKG2Alo natural killer (NK) further increased NK spike protein stimulation. However, impaired with persisting virus. Moreover, also enhanced expression major histocompatibility complex (MHC)-E on macrophages, possibly inhibiting cell-mediated killing. Macaques less mounted adaptive that escaped MHC-E-dependent inhibition. Our findings reveal an interplay between regulated persistence mediated IFN-γ.

Язык: Английский

Процитировано

45
The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5 DOI Creative Commons
Huiping Shuai, Jasper Fuk‐Woo Chan, Bingjie Hu

и другие.

EBioMedicine, Год журнала: 2023, Номер 95, С. 104753 - 104753

Опубликована: Авг. 12, 2023

Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related resulted in largest number of infections. While recent studies demonstrated all robustly escape neutralizing antibody response, it remains unclear on whether these share any pattern evolutionary trajectory replication efficiency intrinsic pathogenicity along respiratory tract.We compared virological features, capacity dominant BA.2 BA.5 human nasal epithelium, characterized K18-hACE2, A129, young C57BL/6, aged C57BL/6 mice.We found replicated most robustly, followed by differentiated epithelium. Consistently, infection higher viral gene copies, infectious titres more abundant antigen expression turbinates infected K18-hACE2 transgenic mice. In contrast, are continuously attenuated lungs mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe sublineages-infected A129 mice.Our results suggested might be gaining fitness upper tract, therefore highlighting importance global surveillance emergence hyper-transmissive sublineages. On contrary, is further lower tract. Effective vaccination other precautions should place prevent infections immunocompromised populations at risk.A full list funding bodies contributed this study can Acknowledgements section.

Язык: Английский

Процитировано

38
Comparative Study of Cytokine Profiles in SARS-CoV-2 Delta and Omicron Variants DOI Open Access
Michaela Krivosova, Juliana Hanusrichterová, Vincent Lučanský

и другие.

Bratislavské lekárske listy/Bratislava medical journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract Background The coronavirus disease 2019 (COVID-19) has highly impacted everyday lives and healthcare systems since its spread across the globe. As a result of numerous mutations in viral genome, several genetic variants sub-variants have evolved, they differ various characteristics, such as infectivity, transmissibility, immune response human body. aim this study was to compare cytokine levels plasma samples from patients with acute COVID-19, infected either Delta or Omicron variants. Methods This retrospective included 80 hospitalized PCR-confirmed SARS-CoV-2. Blood well control subjects were collected, multiplex assay performed determining 48 cytokines plasma. Results 50 Delta, 30 variant, 18 subjects. Severe critical course led 27 significantly modified both COVID-19 compared However, 12 (GRO-α, IFN-α2, IL-1α, IL-4, IL-9, IL-16, MIF, MIP-1β, SDF-1α, TNF-α, TNF-β, TRAIL) elevated versus variant discrimination equal AUC = 0.876. Moreover, vaccination decreased GM-CSF, IL-7, IL-8 variant. Conclusions suggests that SARS-CoV-2 affect differently.

Язык: Английский

Процитировано

1
Combined molnupiravir-nirmatrelvir treatment improves the inhibitory effect on SARS-CoV-2 in macaques DOI Creative Commons
Kyle Rosenke,

Matt C. Lewis,

Friederike Feldmann

и другие.

JCI Insight, Год журнала: 2022, Номер 8(4)

Опубликована: Дек. 27, 2022

The periodic emergence of SARS-CoV-2 variants concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, nirmatrelvir (PF-07321332), 3C-like protease inhibitor, have recently been approved as monotherapy use in high-risk patients COVID-19. As preclinical data are only available rodent ferret models, here we assessed efficacy MK-4482 PF-07321332 alone combination against infection Delta VOC rhesus macaque COVID-19 model. Macaques were infected variant treated vehicle, MK-4482, PF-07321332, or PF-07321332. Clinical exams performed at 1, 2, 4 days postinfection assess disease virological parameters. Notably, improved individual inhibitory effect both drugs, resulting milder progression, stronger reduction virus shedding from mucosal tissues upper respiratory tract, viral replication lower reduced lung pathology. Our strongly indicate superiority combined treatment infections demonstrated closest surrogate model human infection.

Язык: Английский

Процитировано

31
Intra- vs. Interhost Evolution of SARS-CoV-2 Driven by Uncorrelated Selection—The Evolution Thwarted DOI Creative Commons
Mei Hou, Jingrong Shi,

Zanke Gong

и другие.

Molecular Biology and Evolution, Год журнала: 2023, Номер 40(9)

Опубликована: Сен. 1, 2023

Abstract In viral evolution, a new mutation has to proliferate within the host (Stage I) in order be transmitted and then compete population II). We now analyze intrahost single nucleotide variants (iSNVs) set of 79 SARS-CoV-2 infected patients with most transmissions tracked. Here, every two measures: 1) iSNV frequency each individual Stage I; 2) occurrence among individuals ranging from 1 (private), 2–78 (public), (global) occurrences II. I, small fraction nonsynonymous iSNVs are sufficiently advantageous rise high frequency, often 100%. However, such usually fail become public mutations. Thus, selective forces stages evolution uncorrelated and, possibly, antagonistic. For that reason, successful mutants, including many concern, have avoid being eliminated I when they first emerge. As result, may not transmission advantage outcompete dominant strains hence, rare population. Few them could manage slowly accumulate mutations When do, would appear suddenly as six successive waves strains. conclusion, gate-keeper, contravene long-term should heeded studies.

Язык: Английский

Процитировано

21
An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models DOI
Emiko Urano, Yumi Itoh, Tatsuya Suzuki

и другие.

Science Translational Medicine, Год журнала: 2023, Номер 15(711)

Опубликована: Авг. 30, 2023

The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, resulting subvariants display further evasion antibody escape. An engineered angiotensin-converting enzyme (ACE2) decoy composed of high-affinity ACE2 an IgG1 Fc domain could offer alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum therapeutic potential in rodent models. Here, we demonstrate that retains neutralization activity against subvariants, including currently emerging XBB BQ.1 strains, which completely evade antibodies clinical use. SARS-CoV-2, suboptimal concentration neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type monoclonal antibodies, whereas no escape mutant emerged decoy. Furthermore, inhalation aerosolized decoys improved outcomes rodents infected with at a 20-fold lower dose than intravenous administration. Last, exhibited efficacy for cynomolgus macaques These results indicate this represents promising strategy overcome immune-evading variants liquid aerosol be considered as noninvasive approach enhance COVID-19 treatments.

Язык: Английский

Процитировано

19
Characterization of Omicron BA.4.6, XBB, and BQ.1.1 subvariants in hamsters DOI Creative Commons
Peter Halfmann, Kiyoko Iwatsuki‐Horimoto, Makoto Kuroda

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Март 15, 2024

Abstract During the Omicron wave, previous variants such as BA.2, BA.4, and BA.5 were replaced by newer with additional mutations in spike protein. These variants, BA.4.6, BQ.1.1, XBB, have spread different countries degrees of success. Here, we evaluated replicative ability pathogenicity BQ1.1, XBB clinical isolates male Syrian hamsters. Although found no substantial differences weight change among hamsters infected these subvariants, BQ.1.1 lung tissue was higher than that BA.4.6 BA.5. Of note, lethal both female transgenic human ACE2 In competition assays, replicated better nasal turbinate tissues previously BA.2. results suggest subvariants family are still evolving should be closely monitored.

Язык: Английский

Процитировано

6
Olfactory immune response to SARS-CoV-2 DOI Creative Commons
Sebastian A. Wellford, E. Ashley Moseman

Cellular and Molecular Immunology, Год журнала: 2023, Номер 21(2), С. 134 - 143

Опубликована: Дек. 25, 2023

Abstract Numerous pathogens can infect the olfactory tract, yet pandemic caused by SARS-CoV-2 has strongly emphasized importance of mucosa as an immune barrier. Situated in nasal passages, is directly exposed to environment sense airborne odorants; however, this also means it serve a direct route entry from outside world into brain. As result, olfactotropic infections have serious consequences, including dysfunction system, CNS invasion, dissemination lower respiratory and transmission between individuals. Recent research shown that distinctive response needed protect neuronal mucosal tissue. A better understanding innate, adaptive, structural barriers develop effective therapeutics vaccines against microbes such SARS-CoV-2. Here, we summarize ramifications infection mucosa, review subsequent response, discuss important areas future for immunity infectious disease.

Язык: Английский

Процитировано

16
Augmentation of Omicron BA.1 pathogenicity in hamsters using intratracheal inoculation DOI Creative Commons
Julia R. Port, Claude Kwe Yinda,

Claire Ruckel

и другие.

npj Viruses, Год журнала: 2024, Номер 2(1)

Опубликована: Янв. 16, 2024

Abstract The Omicron BA.1 variant of SARS-CoV-2 displays an attenuated phenotype in the Syrian hamster after intranasal inoculation. This is characterized by reduced viral replication and lung pathology lower respiratory tract. Here, we report that intratracheal inoculation with recovers tract pathogenicity as observed other lineages.

Язык: Английский

Процитировано

5