Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

Viruses, Год журнала: 2022, Номер 14(5), С. 1020 - 1020

Опубликована: Май 11, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme (hACE2), we investigated spatiotemporal distribution pathomorphological features in CNS following intranasal infection with SARS-CoV-2 variants, well after prior influenza A virus infection. Apart from Omicron, found all variants to frequently spread within CNS. Infection was restricted neurons appeared olfactory bulb mainly basally oriented regions brain into spinal cord, independent ACE2 expression without evidence neuronal cell death, axonal damage demyelination. However, microglial activation, microgliosis a mild macrophage T dominated inflammatory response consistently observed, accompanied by apoptotic death endothelial, immune cells, their apparent Microgliosis apoptosis indicate potential role microglia for pathogenesis viral effect COVID-19 possible impairment functions, especially long COVID. These data may be informative selection therapeutic candidates broadly support investigation agents adequate penetration relevant

Язык: Английский

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SARS-CoV-2 Infections in Animals: Reservoirs for Reverse Zoonosis and Models for Study

Viruses, Год журнала: 2021, Номер 13(3), С. 494 - 494

Опубликована: Март 17, 2021

The recent SARS-CoV-2 pandemic has brought many questions over the origin of virus, threat it poses to animals both in wild and captivity, risks a permanent viral reservoir developing animals. Animal experiments have shown that variety can become infected with virus. While coronaviruses been known infect for decades, true intermediate host virus not identified, no cases screening wild, farmed, domesticated is necessary help us understand its origins prevent future outbreaks COVID-19 other diseases. There intriguing evidence farmed mink infections (acquired from humans) led infection farm workers turn, outbreak variant humans Denmark. A thorough examination current knowledge ability different animal species therefore vital evaluate human transmission reverse zoonosis.

Язык: Английский

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Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4 ⁺ T Cell Responses

Journal of Virology, Год журнала: 2022, Номер 96(6)

Опубликована: Фев. 2, 2022

Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, immunopathogenic events occurring with coinfections SARS-CoV-2 IAV remain unclear. Here, we report pathogenic immunological consequences H1N1 in K18-hACE2 transgenic mouse model. Compared single infection or IAV, not only prolonged primary period but also increased immune cell infiltration inflammatory cytokine levels bronchoalveolar lavage fluid leading to pneumonia lung damage. Moreover, caused lymphopenia peripheral blood, resulting reduced total IgG, neutralizing antibody titers, CD4

Язык: Английский

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Common Laboratory Mice Are Susceptible to Infection with the SARS-CoV-2 Beta Variant

Viruses, Год журнала: 2021, Номер 13(11), С. 2263 - 2263

Опубликована: Ноя. 11, 2021

Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited this purpose but not susceptible to infection with wild-type SARS-CoV-2. However, the development mouse-adapted virus strains has revealed key mutations in SARS-CoV-2 spike protein that increase infectivity, and interestingly, many these also present naturally occurring variants concern. This suggests might have ability infect common mice. Herein we show beta variant attains infectibility BALB/c causes pulmonary changes within 2-3 days post infection, consistent results seen other murine COVID-19, at a reasonable dose (2 × 10

Язык: Английский

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How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics

Viruses, Год журнала: 2023, Номер 15(6), С. 1303 - 1303

Опубликована: Май 31, 2023

Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% cases, and several simultaneously circulating. Some unique copathogens result reduced pathogenicity, while other pairings can worsen disease. The mechanisms driving these dichotomous outcomes likely variable have only begun to be examined the laboratory clinic. To better understand viral–viral coinfections predict potential that distinct outcomes, we first systematically fit mathematical models load data from ferrets infected respiratory syncytial virus (RSV), followed by influenza A (IAV) after 3 days. results suggest IAV rate RSV production, cell clearance. We then explored realm possible dynamics for scenarios had not been experimentally, including different infection order, coinfection timing, interaction mechanisms, pairings. rhinovirus (RV) or SARS-CoV-2 (CoV2) was using human single together murine weight-loss IAV-RV, RV-IAV, IAV-CoV2 guide interpretation model results. Similar RSV-IAV coinfection, this analysis shows increased severity observed during IAV-RV due slower clearance IAV-infected cells viruses. improved outcome when RV, on hand, could replicated RV IAV. Simulating way provides new insights about how interactions regulate yields testable hypotheses ripe experimental evaluation.

Язык: Английский

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Reassessing the Risk of Severe Parvovirus B19 Infection in the Immunocompetent Population: A Call for Vigilance in the Wake of Resurgence

Viruses, Год журнала: 2024, Номер 16(9), С. 1352 - 1352

Опубликована: Авг. 24, 2024

Despite Parvovirus B19 (B19V) generally causing mild or asymptomatic infections, and only certain high-risk groups such as hematological immunocompromised patients pregnant women tending to develop complications, several factors challenge the assumption of a "benign" clinical course in immunocompetent adults adolescents. A significant proportion population may harbor undiagnosed health conditions genetic predispositions that could render them more susceptible severe B19V complications. These include disorders, immune dysregulation not resulting overt immunodeficiency, underlying cardiac conditions. Concurrent infections with other pathogens, even seemingly minor ones, synergistically increase severity infection, leading pronounced manifestations. While definitively proven, possibility emerging strains increased virulence altered tissue tropism cannot be entirely discounted. Additionally, period pandemic-related restrictions likely led reduced circulation, potentially cohort young limited natural immunity, making vulnerable infection. Potential consequences atypical presentations, individuals without known risk factors. The traditional focus on primarily pediatric concern might lead underdiagnosis delayed diagnosis adults, hindering timely intervention management. surge B19V-related if individually mild, collectively strain healthcare resources, particularly settings capacity pre-existing pressures. Possible recommendations are heighten awareness high index suspicion for infection adolescents presenting compatible symptoms, absence classic expanding testing criteria enhancing public surveillance efforts would prudent.

Язык: Английский

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The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19

Microbiology Spectrum, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

ABSTRACT Immunocompromised individuals are susceptible to severe coronavirus disease 2019 and potentially contribute the emergence of variants with altered pathogenicity due persistent infection. This study investigated impact immunosuppression on acute respiratory syndrome 2 (SARS-CoV-2) infection in K18-hACE2 mice effectiveness antiviral treatments this context during first 7 days Mice were immunosuppressed using cyclophosphamide infected a B lineage SARS-CoV-2. Molnupiravir nirmatrelvir, alone combination, administered, viral load sequence diversity assessed. Treatment but immunocompromised both compounds either singly or combination resulted decreased loads pathological changes compared untreated animals. also abrogated neuronal tissue. However, no consistent consensus observed, except for S:H655Y mutation. Molnupiravir, not nirmatrelvir alone, increased transition/transversion ratio, representative G > A C U mutations, increase was by co-administration molnupiravir. Notably, itself did appear promote mutational characteristics concern (VOCs). Further investigations warranted fully understand role VOC development, especially taking persistence into consideration, inform optimized public health strategies. It is more likely that immunodeficiency promotes does necessarily lead substantial consensus-level absence selection pressure. Consistent mechanisms action, molnupiravir showed stronger mutagenic effect than model. IMPORTANCE The central aim risk-assess administering compound, molnupiravir, patients believed already be at risk generating diversity, which could have implications resistance development. Combination therapy has long history mitigating used demonstrate its potential usefulness context. Animals treated an ratios over time, drug’s mechanism action recent UK-wide phase II clinical trial assessing efficacy humans. addition clearance, turn reduces probability rapid intra-host evolution

Язык: Английский

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The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections

Viruses, Год журнала: 2023, Номер 15(8), С. 1637 - 1637

Опубликована: Июль 27, 2023

The respiratory system is the main target of severe acute syndrome coronavirus 2 (SARS-CoV-2), cause disease 19 (COVID-19) where distress considered leading death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have suggested to play a central role development lung injury. Similar vascular changes are also observed animal models COVID-19. present study aimed determine whether latter specific for SARS-CoV-2 infection, investigating response lungs mice infected with and other viruses (influenza A murine gammaherpesvirus) by situ approaches (histology, immunohistology, morphometry) combined RNA sequencing bioinformatic analysis. Non-selective recruitment monocytes T B cells from larger muscular veins arteries was all viruses, matched comparable transcriptional response. There no evidence endothelial cell infection any models. Both morphological investigation transcriptomics approach support interpretation that vasculature mounts stereotypic alveolar epithelial damage. This may implications treatment management humans.

Язык: Английский

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The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 2024

Synopsis Objectives Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute the emergence of variants with altered pathogenicity due persistent infection. This study investigated impact immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice effectiveness antiviral treatments this context during first 7 days Methods Mice were immunosuppressed using cyclophosphamide infected a B lineage SARS-CoV-2. Molnupiravir nirmatrelvir, alone combination, administered viral load sequence diversity was assessed. Results Treatment but immune compromised both compounds either singly or combination resulted decreased loads pathological changes compared untreated animals. also abrogated neuronal tissue. However, no consistent consensus observed, except for S:H655Y mutation. Molnupiravir, not nirmatrelvir alone, increased transition/transversion (Ts/Tv) ratio, representative A>G C>U mutations increase by co-administration molnupiravir. Notably, itself did appear promote mutational characteristic concern (VOCs). Conclusions Further investigations warranted fully understand role immunocompromised VOC development, especially taking persistence into consideration, inform optimised public health strategies. It is more likely that immunodeficiency promotes does necessarily lead substantial consensus-level absence selection pressure. Consistent mechanisms action, molnupiravir showed stronger mutagenic effect than model.

Язык: Английский

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A random priming amplification method for whole genome sequencing of SARS-CoV-2 virus

BMC Genomics, Год журнала: 2022, Номер 23(1)

Опубликована: Май 30, 2022

Non-targeted whole genome sequencing is a powerful tool to comprehensively identify constituents of microbial communities in sample. There no need direct the analysis any identification before which can decrease introduction bias and false negatives results. It also allows assessment genetic aberrations (e.g., single nucleotide variants, deletions, insertions copy number variants) including noncoding protein regions.

Язык: Английский

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