COVID-19 can directly infect and harm human kidney cells – Science Daily
COVID-19 can directly infect and harm human kidney cells – Science Daily

COVID-19 can directly infect and harm human kidney cells – Science Daily

The virus that causes COVID-19 SARS-CoV-2 can directly infect a specialized type of kidney cells. The discovery helps explain why acute kidney injury is one of the main complications observed in patients with severe COVID-19, according biomedical engineers and virologists at Duke University.

The research appeared online April 20 in the journal Frontiers in Cell and Developmental Biology.

When COVID-19 began to spread across the globe in early 2020, doctors knew that the virus primarily infected cells in the airways. However, as the number of cases began to grow, doctors were surprised to see that many patients – especially those with severe COVID-19 – also developed damage to their kidneys.

The question came to Samira Musah’s attention when she attended a virtual symposium in the spring of 2020. Musah, an assistant professor of biomedical engineering and medicine at Duke, listened while doctors presented research describing how patients who had never experienced any kidney -related problems were developing kidney disease after getting sick with COVID-19.

“It was shocking to hear doctors describe how patients who were healthy suddenly developed a kidney injury and needed dialysis after receiving SARS-CoV-2,” Musah said. “It was clear that the virus was doing something about the kidneys, but it was so early in the pandemic that no one was sure what was going on.”

In previous work, Musah and her team showed that they could guide human-induced pluripotent stem cells to develop and mature into functional podocytes, which are a specific type of kidney cell that helps control the removal of toxins and wastes from the blood. Musah and Titilola Kalejaiye, a postdoctoral fellow in the laboratory, wanted to see if they could use this model to determine how and why SARS-CoV-2 was capable of damaging kidney cells.

As a proof of concept worked Kalejaiye initially with a pseudo-virus version of SARS-CoV-second These psuedovirus is designed to mimic the characteristics of specific viruses, but are unable to produce replication competent viral particles, making them safe to use for wide research. After introducing the pseudo virus in their podocytcellemodel, Kalejaiye discovered that the virus peak protein could bind directly to several receptors on the surface of the podocytes.

“We found that the virus was particularly adept at binding to two key receptors on the surface of the podocytes, and these receptors are abundant in these kidney cells,” explained Kalejaiye, who is also the first author of the paper. “There was a strong uptake of the virus in the beginning, and we also found that when increasing the dose of the virus, the uptake would increase even more. The virus appeared to have a strong affinity for these kidney cells.”

To test their podocyte model with the true SARS-CoV-2 virus, Musah and Kalejaiye teamed up with Maria Blasi, an assistant professor of medicine at Duke and a researcher at the Duke Human Vaccine Institute. Before the pandemic, Blasi explored how viruses, including HIV, infect and damage another subset of kidney cells called renal tubular epithelial cells.

“It was a stroke of luck that we crossed paths at the faculty meeting we both attended,” Blasi said. “Samira was looking for someone with experience in dealing with live viruses, and I was looking for a model of the podocytes that Samira can make, so we decided to beat two birds with one stone.”

As with pseudovirus, the team that live version of the virus noticed had a strong affinity for podocytes. When virus-infected cells, it damaged the podocytes, causing their long, finger-like structures, which help filter blood, to pull and wither. If the damage to the cells was too severe, the podocytes would die.

“In addition to the structural damage, we saw that the virus could hijack the machinery of the podocytes to produce additional viral particles that could spread and infect additional cells,” Blasi said.

Now the team hopes to expand their work by studying how the different variants of SARS-CoV-2 behave in kidney cells. As variants of the virus have emerged, kidney damage occurs less frequently. This has led the team to question how the new variants change and whether they become less able to infect kidney cells.

“I think it’s remarkable that we went from being at home and hearing the first reports from doctors to forming this collaboration virtually and having these results on such a short timeline,” Musah said. “We had the right people and the right tools at the right time. It has been one of the most successful collaborations in my relatively young laboratory, and I look forward to continuing this work.”

This work was supported by a Whitehead Scholarship in Biomedical Research, a Chair’s Research Award from the Department of Medicine at Duke University, a Duke MEDx Pilot Grant on Biomechanics in Injury or Injury Repair, a Burroughs Welcome Fund PDEP Career Transition Ad Hoc Award, a Genentech Research Award, and a George M. O’Brien Kidney Center Pilot Grant (P30 DK081943) awarded to Musah. Blasi was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant number R01DK130381. Work on live SARS-CoV-2 isolate was performed under Biosafety Level 3 (BSL3) at the Duke Regional Biocontainment Laboratory (RBL), which received partial support for construction from the National Institutes of Health, National Institute of Allergy and Infectious Diseases (UC6-) AI058607, G20-AI167200).

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