SARS-CoV-2, a novel coronavirus that causes the COVID-19 disease, can infect enterocytes in the intestine and multiply there, according to a study by researchers from the Netherlands.
Transmission electron microscopy analysis of SARS-CoV-2 infected intestinal organoids: (a to h) overview of an intact organoid (a) showing the onset of virus infection (b to d) at different stages of the viral lifecycle, i.e., early double membrane vesicles (DMVs); (e), asterisk, initial viral production in the Golgi apparatus (f and g) and complete occupation of virus particles inside the endomembrane system (h); (i to k) extracellular viruses are observed in the lumen of the organoid (i), and are found at the basal (j) and apical side (k) alongside the microvilli (arrows). Scale bars – 10 μm (a), 2.5 μm (b to d), 250 nm (e), (f), and (h to k) and 100 nm (g). (l to q) Overview of an organoid (l) showing severely infected cells (m and o), disintegrated cells (o) and stressed cells as evident from the atypical nucleoli (p); intact cells reveal DMV areas of viral replication (p), asterisks, and infected Golgi apparatus (q); (r) extracellular clusters of viruses. Scale bars – 10 μm (l), 2.5 μm (m to p) and 250 nm (p to r). Image credit: Lamers et al, doi: 10.1126/science.abc1669.
Patients with COVID-19 show a variety of symptoms associated with respiratory organs — such as coughing, sneezing, shortness of breath, and fever — and the disease is transmitted via tiny droplets that are spread mainly through coughing and sneezing.
One third of the patients however also have gastrointestinal symptoms, such as nausea and diarrhea.
In addition, the SARS-CoV-2 virus can be detected in human stool long after the respiratory symptoms have been resolved. This suggests that the virus can also spread via so-called fecal-oral transmission.
Though the respiratory and gastrointestinal organs may seem very different, there are some key similarities.
A particularly interesting similarity is the presence of ACE2 (angiotensin converting enzyme 2), the receptor through which SARS-CoV-2 can enter the cells.
The inside of the intestine is loaded with ACE2 receptors. However, until now it was unknown whether intestinal cells could actually get infected and produce virus particles.
Dr. Hans Clevers and colleagues from the Hubrecht Institute, the Erasmus Medical Center and Maastricht University set out to determine whether the SARS-CoV-2 virus can directly infect the cells of the intestine, and if so, whether it can replicate there as well.
The researchers used human intestinal organoids — tiny versions of the human intestine that can be grown in the lab.
“These organoids contain the cells of the human intestinal lining, making them a compelling model to investigate infection by SARS-CoV-2,” Dr. Clevers said.
When the scientists added the virus to the organoids, they were rapidly infected.
Using electron microscopy, they found virus particles inside and outside intestinal enterocytes.
They investigated the response of enterocytes to the virus with RNA sequencing and found that the interferon stimulated genes were activated.
They also cultured the organoids in different conditions that result in cells with higher and lower levels of the ACE2 receptor.
To their surprise, they found that the virus infected cells with both high and low levels of the ACE2 receptor.
“The observations made in this study provide definite proof that SARS-CoV-2 can multiply in cells of the gastrointestinal tract,” said Dr. Bart Haagmans, a researcher in the Viroscience Department at the Erasmus Medical Center.
“However, we don’t yet know whether SARS-CoV-2, present in the intestines of COVID-19 patients, plays a significant role in transmission.”
“Our findings indicate that we should look into this possibility more closely.”
The results were published in the journal Science.
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Mart M. Lamers et al. SARS-CoV-2 productively infects human gut enterocytes. Science, published online May 1, 2020; doi: 10.1126/science.abc1669
Source link: https://www.sci.news/medicine/sars-cov-2-coronavirus-gut-enterocytes-08392.html
