Biology subjects

Power, U.

Publications and source records attributed to Power, U..

3 recordsLinked to original sources

bioRxiv2024

Myoferlin is an essential component of late-stage vRNP trafficking vesicles for enveloped RNA viruses.

The Rab11a endosomal recycling pathway is exploited by important respiratory RNA viruses such as IAV and RSV, aiding viral egress from the apical surface of polarized epithelial cells. Late in infection, Rab11a-containing vesicles specifically transport viral ribonucleoprotein (vRNP) complexes towards the cell surface before packaging and budding. Rather than employing traditional Rab11a-positive recycling endosomes, virus-infected cells generate remodelled Rab11a-containing vesicles, as observed during IAV infection. Besides Rab11a, no other conserved host co-factors have been identified among these various vRNP trafficking vesicles. Here we discovered and confirmed myoferlins association with IAV vRNPs in the cytoplasm and colocalisation with Rab11a during late stages of infection. We also found that this role was conserved in late-stage vRNP trafficking of other viruses, including RSV and SeV. Myoferlin likely recruits the EHD family of proteins, which are involved in endosomal biogenesis, to these unique vRNP trafficking endosomes, highlighting myoferlins pivotal role in viral replication.

microbiology↗

bioRxiv2021

An Endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and went on to cause over 3.3 million deaths in 15 months. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFN{lambda}) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) model from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFN{lambda} expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK/STAT pathway in WD-PNECs with high endogenous IFN{lambda} secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFN{lambda} treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFN{lambda} response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans. Importantly, our work supports the continued exploration of IFN{lambda} as a potential pharmaceutical against SARS-CoV-2 infection.

immunology↗

bioRxiv2018

Characterisation of morphological differences in well-differentiated nasal epithelial cell cultures from preterm and term infants at birth and one-year.

BackgroundInnate immune responses of airway epithelium are important defences against respiratory pathogens and allergens. Newborn infants are at greater risk of severe respiratory infections compared to older infants. However, very little is known regarding human neonatal airway epithelium immune responses and whether age-related morphological and/or innate immune changes contribute to the development of airway disease.\n\nMethodsWe collected nasal epithelial cells from 41 newborn infants (23 term, 18 preterm) within 5 days of birth. Repeat sampling was achieved for 24 infants (13 term, 11 preterm) at a median age of 12.5 months. Morphologically and physiologically authentic well-differentiated primary paediatric nasal epithelial cell (WD-PNEC) cultures were generated and characterised using light microscopy and immunofluorescence.\n\nResultsWD-PNEC cultures were established for 15/23 (65%) term and 13/18 (72%) preterm samples at birth, and 9/13 (69%) term and 8/11 (73%) preterm samples at one-year. Newborn and infant WD-PNEC cultures demonstrated extensive cilia coverage, mucous production and tight junction integrity. Newborn WD-PNECs took significantly longer to reach full differentiation and were noted to have much greater proportions of goblet cells compared to one-year repeat WD-PNECs. No differences were evident in ciliated/goblet cell proportions between term- and preterm-derived WD-PNECs at birth or one-year old.\n\nConclusionWD-PNEC culture generation from newborn infants is feasible and represents a powerful and exciting opportunity to study differential innate immune responses in human airway epithelium very early in life.

immunology↗