Coronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse
lung injuries. The Spike
protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-
inflammations in
COVID-19 is not well known.
Methods and Findings: In this study, we developed a Spike
protein-pseudotyped (Spp) lentivirus with the proper tropism of
SARS-CoV-2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving
intravenous injection of the virus. A lentivirus with
vesicular stomatitis virus glycoprotein (VSV-G) was used as the control. Two hours post-
infection (hpi), Spp showed more than 27-75 times more viral burden in the lungs than other organs; it also exhibited about 3-5 times more viral burden than VSV-G lentivirus in the lungs, liver, kidney and spleen. Acute
pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+ macrophages and pneumocytes in the lungs, but not in MARC1+ macrophages.
IL6,
IL10, CD80 and
PPAR-γ were quickly upregulated in response to
infection of Spp lentivirus in the lungs in vivo as well as in macrophage-like RAW264.7 cells in vitro. We further confirmed that forced expression of the Spike
protein in RAW264.7 cells could significantly increase the
mRNA levels of the same panel of inflammatory factors.
Conclusions: Our results demonstrate that the Spike
protein of SARS-CoV-2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.