Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences DOI Creative Commons
Nan W. Hultgren, Anton Petcherski, Simona Torriano

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(12)

Published: Nov. 28, 2024

Abstract As the SARS-CoV-2 coronavirus continues to evolve and infect global population, many individuals are likely suffer from post-acute sequelae of infection (PASC). Manifestations PASC include vision symptoms, but little is known about ability impact retinal cells. Here, we demonstrate that can perturb pigment epithelium (RPE) in vivo, after intranasal inoculation a transgenic mouse model infection, cell culture. Separate lentiviral studies showed Spike protein mediates viral entry replication RPE cells, while Envelope ORF3a proteins induce morphological changes. Infection with major variants compromised barrier function phagocytic capacity. It also caused complement activation production cytokines chemokines, resulting an inflammatory response spread across layer. This signature has similarities associated onset age-related macular degeneration (AMD), cause human blindness, pathology eventually leads photoreceptor loss. Thus, our findings suggest may have long-term implications for vision, perhaps comparable increased occurrence AMD found among infected by HIV, greater public health consequences due much larger number infections.

Language: Английский

The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection DOI Creative Commons

Vanessa Rivero,

Julia Carrión-Cruz,

Darío López-García

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Oct. 4, 2024

Innate immune responses are induced after viral infections, being these essential to establish an antiviral response in the host. The RIG-I-like receptors (RLRs), RIG-I and MDA5 pivotal for virus detection by recognizing RNAs cytoplasm of infected cells, initiating responses. However, since excessive can have a negative effect on host, regulatory feedback mechanisms needed. In this work, we describe that IFN alpha-inducible protein 27 (IFI27) co-immunoprecipitates with melanoma differentiation-associated 5 (MDA5), interaction likely mediated RNAs. addition, using IFI27 overexpression, knock-out, knock-down show inhibits oligomerization activation, counteracting innate SARS-CoV-2 infections or polyinosinic-polycytidylic acid (poly(I:C)) transfection. Furthermore, our data indicate competes poly(I:C) binding, providing explanation inhibiting activation. This new function could be used design target-driven compounds treat diseases associated exacerbated induction responses, such as those SARS-CoV-2.

Language: Английский

Citations

1
Dimming the corona: studying SARS-coronavirus-2 at reduced biocontainment level using replicons and virus-like particles DOI Creative Commons
Grace Neilsen,

Asha Maria Mathew,

J.M. Castro

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

The coronavirus-induced disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, has had a devastating impact on millions of lives globally, with mortality rates and catastrophic social implications. Developing tools for effective vaccine strategies platforms is essential controlling preventing the recurrence such pandemics. Moreover, molecular virology that facilitate study viral pathogens, mutations, interactions various host proteins are essential. Viral replicon- virus-like particle (VLP)-based systems excellent examples tools. This review outlines importance, advantages, disadvantages both VLP-based have been developed SARS-CoV-2 helped scientific community in dimming intensity COVID-19 pandemic.

Language: Английский

Citations

0
Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences DOI Creative Commons
Nan W. Hultgren, Anton Petcherski, Simona Torriano

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(12)

Published: Nov. 28, 2024

Abstract As the SARS-CoV-2 coronavirus continues to evolve and infect global population, many individuals are likely suffer from post-acute sequelae of infection (PASC). Manifestations PASC include vision symptoms, but little is known about ability impact retinal cells. Here, we demonstrate that can perturb pigment epithelium (RPE) in vivo, after intranasal inoculation a transgenic mouse model infection, cell culture. Separate lentiviral studies showed Spike protein mediates viral entry replication RPE cells, while Envelope ORF3a proteins induce morphological changes. Infection with major variants compromised barrier function phagocytic capacity. It also caused complement activation production cytokines chemokines, resulting an inflammatory response spread across layer. This signature has similarities associated onset age-related macular degeneration (AMD), cause human blindness, pathology eventually leads photoreceptor loss. Thus, our findings suggest may have long-term implications for vision, perhaps comparable increased occurrence AMD found among infected by HIV, greater public health consequences due much larger number infections.

Language: Английский

Citations

0