Tag: ACE2

More ACE2 Makes Pancreatic Cells a COVID Target

Source: CDC

Researchers have revealed insights into how SARS-CoV-2 attacks the insulin-producing cells of the pancreas.

There is mounting evidence of damage to the pancreas and resulting diabetes attributed to COVID, which is of great concern. The virus targets the angiotensin converting enzyme 2 (ACE2) protein on the surface of those cells, and is the subject of a special presentation at this year’s Annual Meeting of the European Association for the Study of Diabetes, given by the University of Siena’s Professor Francesco Dotta. 

“The SARS-CoV-2 virus attacks specific host tissues because of the presence of viral receptors on the surface of the target cells. As such, virus binding to ACE2 protein is the key determinant for its entry, propagation and transmissibility,” explained Prof Dotta.

“Multiple studies have shown that older adults and those with chronic medical conditions like heart and lung disease and/or diabetes are at the highest risk for complications from SARS-CoV-2 infections. Moreover, impaired blood sugar control is associated with increased risk of severe COVID, suggesting a link between COVID infection and diabetes. Several reports indicate a wide, although variable, distribution of the ACE2 protein among different tissues.”

Prof Dotta and colleagues studied the ACE2 expression pattern in pancreatic tissue samples of non-diabetic multiorgan donors to better understand the molecular link between COVID and diabetes.

In the ‘normal’ pancreas, ACE2 is highly expressed in microvasculature and in ductal cells. “Importantly, we found that ACE2 was expressed in human pancreatic islets, where it is preferentially expressed in insulin producing beta-cells. We also demonstrated that ACE2 levels were increased under pro-inflammatory conditions, thus confirming the link between inflammation and ACE2 also in pancreatic islet beta cells.”

In order to isolate the mechanism involved in the upregulation of ACE2 induced by inflammation, ACE2 levels were measured in human pancreatic islets pre-treated with Jak1/2 and TYK2 inhibitors, which block inflammation in beta cells, and then exposed to pro-inflammatory conditions. 

Prof Dotta said: “We showed that these drugs prevent the ACE2 increase induced by inflammation in human pancreatic islets, demonstrating that SARS-CoV-2 receptor ACE2 is regulated through specific molecular pathways and that its increased expression can be prevented.

“We studied the mechanisms of SARS-CoV-2 virus entry into insulin producing beta cells and we discovered that these cells express the SARS-CoV-2 receptor ACE2.” Other authors have independently confirmed such data.

Of note, additional published data confirmed that SARS-CoV-2 can indeed infect pancreatic insulin-producing cells causing their dysfunction or death. Moreover, during inflammation, ACE2 expression increases several times above standard values.

Prof Dotta concluded: “This means that these insulin-producing beta cells could be even more susceptible to viral infection when inflamed. This finding is also important from a clinical standpoint, since keeping inflammatory status under control in patients with COVID may reduce the expression of ACE2 receptor in beta cells with beneficial effects on blood sugar and metabolic control of patients.”

Source: EurekAlert!

Loss of Smell and Taste in COVID Explained

Cut lemon. Photo by Karolina Grabowska from Pexels

New research awaiting peer review uncovers why the loss of sense of taste is one of the symptoms of COVID infection.  New research has found that taste receptors have ACE2 and are also at risk for SARS-CoV-2 invasion.

Understanding the presence of viral infection in taste buds could help treat people with ‘long COVID’ who could continue to experience changes in or loss of taste months after the initial infection.

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) enzyme attached to the membranes of cells as their point of entry. ACE2 enzymes are present all over the body, especially in the lungs and nose, coinciding with COVID’s early symptoms of loss of smell and difficulty breathing. Loss of taste is another early COVID infection sign, although the mechanism behind this is unclear. 

“By demonstrating the co-localization of SARS-CoV-2 virus, Type II taste cell marker, and the viral receptor ACE2, we show evidence for replication of this virus within taste buds that could account for acute taste changes during active COVID-19,” wrote the authors. “This work also shows that the proliferation of the taste stem cells in recovering patients may take weeks to return to their pre-COVID-19 state, providing a hypothesis for more chronic disruption of taste sensation, reports of which are now appearing in the medical literature.”

Source: Wikimedia. CC0 Creative Commons
Diagram of the tongue. The fungiform papillae is located near the centre of the tongue.

ACE2 is present on Type II taste bud cells on the tongue. There are three cranial nerves (CN VII, IX and X) that are involved in relaying taste information to the central nervous system. Taste is first discriminated in taste receptor cells (TRCs) within taste buds located in circumvallate (CVP), foliate (FLP) and fungiform papillae (FP) in the tongue. Three defined TRCs relay five basic tastes. Stem cells around the taste bud receive signals from taste cells, prompting differentiation into a replacement TRC. 

The researchers identified 5000 to 10 000 taste buds, with almost half located at the base of the tongue called circumvallate papillae. ACE2 was found to be coexpressed with phospholipase C β2 used in the signaling of type II taste receptor cells. Taste receptor cells in the back of the tongue, a region known as fungiform pallipae, also had ACE2 receptors, providing further evidence of a viral entry point for SARS-CoV-2.

“Replication of virus can likely then occur undisturbed and allow for transmission from the taste bud into circulation, and locally infect lingual and salivary gland epithelium, oral mucosa and larynx and even on into the lungs,”

Case Studies of Altered Taste During and After COVID Infection

A 45-year old woman with COVID and controlled hypertension reported changes in her sense of taste, including not being able to taste the sweetness from chocolate and describing curry as ‘white’ and her tongue was enlarged and redder around the fusiform pallipae.

SARS-CoV-2 RNA was found in samples taken from that area, specifically in PLCB2 positive cells. The virus was also found in the lamina propria with disruptions in the stem cell layer. Symptoms improved after six weeks, along with taste perception.

A 63-year-old man with no preexisting conditions had donated samples of his fusiform pallipae in 2019, and more samples were taken six weeks after testing positive for COVID. He experienced several long COVID symptoms, including mild loss of taste — coffee tasted like mud, and he could not taste chocolate. The virus was not present in samples of his fusiform pallipae 10 weeks after infection. However, he had altered changes to the stem cell layer of the tongue compared to the 2019 samples.

The researchers suggested that stem cell impairments may affect taste bud cell turnover and could contribute to the delayed return of sense of taste.

Source: News-Medical.Net

Journal information: Doyle ME, et al. Human Taste Cells Express ACE2: a Portal for SARS-CoV-2 Infection. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.04.21.440680
https://www.biorxiv.org/content/10.1101/2021.04.21.440680v1