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Combating SARS-CoV-2 with Natural Killer Cells

Research project launched at the German Primate Center and the University of Düsseldorf
Infection with cytomegaloviruses (CMV) causes the body to produce long-lived, adaptive natural killer cells (NK cells) in one third of infected people. How these cells fight an infection with SARS-CoV-2 is being investigated in a joint project of the German Primate Center and the University of Düsseldorf. Figure: Lutz Walter
Prof. Dr. Lutz Walter, Leiter der Abteilung Primatengenetik am Deutschen Primatenzentrum in Göttingen. Foto: Karin Tilch
Prof. Dr. Lutz Walter, Head of the Primate Genetics Laboratory at the German Primate Center in Göttingen. Photo: Karin Tilch

Cold sores, chicken pox, shingles - these are only three particularly well-known examples of diseases caused by herpesviruses. Infection with herpesviruses is usually chronic, i.e. one cannot get rid of these viruses and carries them throughout one's life. A lesser-known member of the herpesvirus family is the cytomegalovirus (CMV), which is usually inconspicuous in people with a functioning immune system. CMV infection is highly prevalent worldwide, with between 30 and 100 percent of the population infected, depending on the region. In one third of infected individuals, CMV leaves a "fingerprint" in the immune system. This is particularly evident in the natural killer (NK) cells, which are lymphocytes and belong to the innate immune system. The NK cells can recognize and specifically kill virus-infected cells and thus counteract an existing infection. The fingerprint becomes evident by formation of so-called adaptive NK cells, which are long-lived and can react more quickly to a resurgence of CMV viruses lying dormant in the body. These adaptive properties are usually found in antibody producing B lymphocytes and in T lymphocytes, where they are referred to as immunological memory.

Lutz Walter, head of the Primate Genetics Laboratory at the German Primate Center - Leibniz Institute for Primate Research, and Markus Uhrberg of the Institute of Transplantation Diagnostics and Cell Therapeutics at the University of Düsseldorf, want to study adaptive NK cells in more detail. The two researchers want to find out whether the adaptive NK cells induced by CMV infection have a positive or negative role in the disease process in COVID-19. For this purpose, adaptive NK cells will be obtained from blood samples of SARS-CoV-2 patients with mild or with severe disease progression, respectively, and functionally investigated. In parallel, adaptive NK cells from blood samples of rhesus monkeys will be analyzed. These blood samples originate from SARS-CoV-2 infection experiments with rhesus monkeys in the context of other research projects at the DPZ. "We hope that our results will not only help us learn more about adaptive NK cells, but also provide us with a method to relatively easily predict disease progression in COVID-19 in CMV-positive patients," says Lutz Walter. This tandem project is funded under the DFG focus grant COVID-19 "Immunity, host susceptibility and pathomechanisms of infection with SARS-CoV-2".