Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in Chronic Obstructive Pulmonary Disease

Abstract

SARS-CoV-2 or COVID-19’s first case was discovered in December 2019 in Wuhan, China, and by March 2020 it was declared a pandemic by the WHO. It has been shown that various underlying conditions can increase the chance of having severe COVID-19.

Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2

“…However, we found that the IS4 "NSPR" created a pat7 NLS "PRRARSV" in the S protein, which was unique to SARS-CoV-2. We first reported that the S protein translocated into the nucleus in the SARS-CoV-2-infected airway epithelium, which is an appropriate lung model for studying respiratory virus infection in vitro [2,43]. Our results confirmed that the SARS-CoV-2 S protein was a unique addition to the list of viral proteins that possess NLSs and consequently translocate into the nucleus of infected cells [17,30,31,44].…”

“…In this study, we used cells from five donors: nonsmoker healthy adults (donors #1 and #2) and adult with chronic obstructive pulmonary disease (COPD) (donor #3). The protocols for subculturing primary NHBE cells were published previously [2, 43, 50]. SARS-CoV-2 (USA/WA-CDC-WA1/2020 isolate, GenBank accession no.…”

“…All viral infection experiments were conducted in the high biocontainment facility at RML, NIAID, NIH, Hamilton, MT. After approximately 3 weeks, the differentiated airway epithelium on Transwells was shipped to RML in an optimized transportation medium [2, 50], and the recovered cells were maintained in complete ALI medium for approximately one week before infection. For infection, the airway epithelium on Transwells was washed with 200 µl of 1x PBS to remove mucus and were infected on the apical site with SARS-CoV-2, MERS-CoV, or SARS-CoV at a MOI of 0.1 in 100 µl 1x PBS for 1 hour (at 37°C with 5% CO 2 ).…”

“…Complete ALI medium (1000 µl) was added to the lower chamber of each Transwell, and the upper chamber was kept empty. Mock-infected and virus-infected Transwells were incubated for 4 days at 37°C in an incubator with 5% CO 2 [2].…”

“… Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2.…”