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PLoS Pathogens ; 18(8):e1010349, 2022.
Article in English | MEDLINE | ID: covidwho-2021976


SARS-CoV-2 is a betacoronavirus and the etiological agent of COVID-19, a devastating infectious disease. Due to its far-reaching effect on human health, there is an urgent and growing need to understand the viral molecular biology of SARS-CoV-2 and its interaction with the host cell. SARS-CoV-2 encodes 9 predicted accessory proteins, which are presumed to be dispensable for in vitro replication, most likely having a role in modulating the host cell environment to aid viral replication. Here we show that the ORF6 accessory protein interacts with cellular Rae1 to inhibit cellular protein production by blocking mRNA export. We utilised cell fractionation coupled with mRNAseq to explore which cellular mRNA species are affected by ORF6 expression and show that ORF6 can inhibit the export of many mRNA including those encoding antiviral factors such as IRF1 and RIG-I. We also show that export of these mRNA is blocked in the context of SARS-CoV-2 infection. Together, our studies identify a novel mechanism by which SARS-CoV-2 can manipulate the host cell environment to supress antiviral responses, providing further understanding to the replication strategies of a virus that has caused an unprecedented global health crisis.

FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821854


In March 2020, TTUHSC opened a new 20,000sf Institute of Anatomical Sciences for human gross anatomy. When the COVID-19 pandemic struck and many schools shifted from in person to online teaching, we hypothesized that if safety measures were used, in person cadaveric anatomy could be safely taught without a decrease in student performance. To test this, we reduced onsite attendance to less than 25% of room capacity. Masks were required at all times and students were instructed to social distance. Six students were assigned per cadaver, but only two students dissected at a time. The other four students reviewed and completed dissections and/or reviewed in groups of two at other allotted times. Thus, students dissected only every third lab. Dissection and lab review attendance was mandatory and students were nearly 100% compliant. Teaching assistants recorded dissected prosections reviews, and these videos were uploaded to password protected course files for independent learning. Students were provided iPads in the laboratory and access to three software packages for use on and off site. All students had access to multiple formative quizzes and exams, and three new online practice practical exams were created. To help reduce testing anxiety, a pass/fail system replaced categorical grading. However, all written and practical exams were conducted on site and in person. At TTUHSC, we have developed an exam question database to track historical student performance including a 25-question optional pre-block practice exam used to assess incoming student anatomical aptitude. In 2020, 90% of incoming students (93% in 2019) took the pre-block exam and scored an average of 28% (24% in 2019). In 2020, despite vastly different content delivery approaches (>80% of lectures were on Zoom) and reduced in-person dissection requirements, students modestly outperformed their 2019 counterparts. Overall exam averages were 89% in 2020 compared to 87% in 2019. If a categorical system was in place, 66% of students would have earned Honors or High Pass in 2020 compared to 61% in 2019. Our formative assessments were highly predictive of summative exam performance, and students reported that they reduced exam stress. Furthermore, summative exam averages correlated strongly with NBME performance (p<0.0001, r =0.63). TTUHSC medical students estimated that a majority of their peers at other medical schools did not have any in person dissection in 2020. Our students ranked in person laboratory dissection as the most useful learning activity, 88% reported that our COVID-19 preparations were very good to outstanding, and 97% were satisfied with the quality of their anatomy education. We conclude that 1) When using appropriate precautions, in person cadaveric anatomy can be taught safely during a pandemic;2) cadaveric dissection is essential for mastery of anatomical concepts;and 3) coupling online learning modalities with rigorous formative assessments prevented a modest reduction in cadaveric dissection opportunities from negatively impacting student performance. 2.

Eurosurveillance ; 26(29):10, 2021.
Article in English | Web of Science | ID: covidwho-1341599


Background In South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter. Methods We assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019. Results Facility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced;however, an increase in RSV detection was observed after the typical season, following the reopening of schools and the easing of measures. Conclusion COVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.