Publications by authors named "Hanako Reyes"

Unlabelled: Double-stranded RNA (dsRNA) is a pathogen associated molecular pattern recognized by multiple pattern recognition receptors and induces innate immune responses. Viral infections can generate dsRNA during virus replication. Genetic mutations can also lead to endogenous dsRNA accumulation.

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Infection with the flavivirus Zika virus (ZIKV) can result in tissue tropism, disease outcome, and route of transmission distinct from those of other flaviviruses; therefore, we aimed to identify host machinery that exclusively promotes the ZIKV replication cycle, which can inform on differences at the organismal level. We previously reported that deletion of the host antiviral ribonuclease L (RNase L) protein decreases ZIKV production. Canonical RNase L catalytic activity typically restricts viral infection, including that of the flavivirus dengue virus (DENV), suggesting an unconventional, proviral RNase L function during ZIKV infection.

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Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection; induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung; and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease.

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The COVID-19 pandemic poses a serious global health threat. The rapid global spread of SARS-CoV-2 highlights an urgent need to develop effective therapeutics for blocking SARS-CoV-2 infection and spread. imulator of terferon enes (STING) is a chief element in host antiviral defense pathways.

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Article Synopsis
  • Coronaviruses, including SARS-CoV-2, have developed ways to dodge the body's antiviral defenses, particularly those triggered by viral double-stranded RNA, such as interferon (IFN) signaling and OAS-RNase L pathways.
  • In studies of SARS-CoV-2 across various cell types, including nasal epithelial cells and lung cells, a weak IFN response was noted, though PKR and OAS-RNase L pathways were activated, indicating some level of host immune response.
  • Unlike other coronaviruses that successfully inhibit host defenses, SARS-CoV-2 does not completely block these antiviral pathways, which may play a role in its unique impact on disease severity and progression.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/).

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